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Information on EC 3.4.24.69 - bontoxilysin and Organism(s) Clostridium botulinum and UniProt Accession P10844
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3.4.24.69 bontoxilysinSpecify your search results
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- 3.4.24.69
- pain
- nerve
- spastic
- dystonias
-
bonts
-
facial
- palsy
- bladder
-
overact
- limb
- botulism
- paralysis
- neuromuscular
- spasm
-
placebo
-
double-blinded
- headache
- detrusor
- migraine
- incontinence
-
cosmetic
-
relief
-
rehabilitation
-
placebo-controlled
-
neurogenic
-
sphincter
-
satisfaction
-
aesthetic
- dysphagia
- snap-25
- ptosis
-
involuntary
-
anticholinergic
- eyelid
- strabismus
-
intravesical
-
wrinkle
-
urodynamic
-
electromyography
- flexor
- masseter
- voice
-
rectus
- fissure
-
filler
- adductor
- antitoxin
-
physiotherapy
-
pneumatic
- baclofen
- molecular biology
- medicine
- drug development
- analysis
The taxonomic range for the selected organisms is: Clostridium botulinum
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
Synonyms
botulinum toxin, botulinum toxin type a, bont-a, bont/a, onabotulinumtoxina, botulinum neurotoxin, bonta, incobotulinumtoxina, bont/b, abobotulinumtoxina, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
BoNT/B
BoNT
BoNT F
BoNT serotype A
BoNT-A
BoNT/A
BoNT/A LC
BoNT/A1
BoNT/A2
BoNT/A3
BoNT/A4
BoNT/A5
BoNT/B
BoNT/C1
BoNT/CD
BoNT/D
BoNT/E
BoNT/F
BoNT/F5
BoNT/G
BoNTE
Bontoxilysin C1
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-
-
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Botulinum neurotoxin
botulinum neurotoxin a
botulinum neurotoxin A subtype 1
botulinum neurotoxin B
botulinum neurotoxin serotype A
botulinum neurotoxin serotype A light chain
botulinum neurotoxin serotype F
botulinum neurotoxin type A
botulinum neurotoxin type B
botulinum neurotoxin type D
botulinum neurotoxin type F
botulinum toxin
Clostridium botulinum neurotoxin serotype A
Clostridium botulinum neurotoxin type E
LCA
LHn/D
catalytic and translocation domain of botulinum neurotoxin type D
type A botulinum neurotoxin
additional information
BoNT
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-
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BoNT
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BoNT/A
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649916, 651236, 670172, 670417, 670666, 683069, 683245, 683671, 710852, 710928, 710941, 711067, 711103, 711531, 712133, 712151, 712247, 712515, 712698, 712755, 712808, 712809, 712844, 712846, 712852, 713171, 713345, 713346, 713458, 713553, 713554, 713556, 713557, 718742, 719043, 719089, 719928, 720811, 720979, 733970, 734225, 752595, 753000, 754424, 755325, 755510, 755601
BoNT/B
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-
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BoNT/B
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BoNT/C1
-
-
-
-
BoNT/D
-
-
-
-
BoNT/E
-
-
-
-
BoNT/E
-
-
BoNT/F
-
-
-
-
BoNT/G
-
-
-
-
Botulinum neurotoxin
-
-
-
-
Botulinum neurotoxin
-
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Botulinum neurotoxin
-
a group of proteins produced by different strains of Clostridium botulinum, that are responsible for botulism disease
botulinum neurotoxin a
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-
botulinum neurotoxin B
-
-
botulinum neurotoxin serotype A
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botulinum neurotoxin type A
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type A botulinum neurotoxin
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-
additional information
-
botulinum neurotoxins, BoNTs, constitute a family of seven structurally similar but antigenically distinct proteins produced by different strains of Clostridium botulinum
additional information
-
Clostridium botulinum C2 toxin belongs to the family of binary AB type toxins
additional information
BoNT from Clostridium botulinum OFD05, isolated from bovine botulism in Japan, is a D/C mosaic-type BoNT
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
mechanism
-
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
reaction mechanism
P10845
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
structure/function relationship
-
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
active site structure and structure-function relationship
-
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
enzyme-substrate interaction at the active site, Tyr366 and Arg363 are important for catalysis, the S1' site is formed by Phe194, Thr215, Thr220, Asp370, and Arg363, reaction mechanism, overview
P10845
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
mechanism of action of botulinum neurotoxin, botulinum toxin binds to a receptor on the neuronal surface, e.g. SV2 receptor for BoNT/A, or synaptotagmin I and II for BoNT/B and BoNT/G, and is subsequently internalized through endocytosis, schematic overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
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CAS REGISTRY NUMBER
COMMENTARY
107231-12-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
VAMPTide + H2O
?
substrate for subtype BoNT/B
-
-
?
5-carboxyfluorescein-TRIDEANQRATK-Dabcyl-6-aminohexanoic acid-CONH2 + H2O
?
-
-
-
-
?
5-carboxyfluorescein-TRIDEANQRATK-Dabcyl-norleucine-CONH2 + H2O
?
-
-
-
-
?
7-hydroxy-4-methylcoumarin-3-acetyl-TRIDEANQRATK-Dabcyl-6-aminohexanoic acid-CONH2 + H2O
?
-
-
-
-
?
7-hydroxy-4-methylcoumarin-3-acetyl-TRIDEANQRATK-Dabcyl-CONH2 + H2O
?
-
-
-
-
?
7-hydroxy-4-methylcoumarin-3-acetyl-TRIDEANQRATK-Dabcyl-norleucine-CONH2 + H2O
?
-
-
-
-
?
Ac-ERDQKLSELDDRADALQAG-(7-methoxy-4-methylcoumaryl)Lys-SQ-diaminopropionic acid(2,4-dinitrophenyl)-ESSAAKLKRKYWWKNLK-NH2 + H2O
?
-
development of a FRET peptide substrate, based on the native substrate binding site of human VAMP2 residues 55-94, and evaluation for enzymatic cleavage by the BoNT/B light chain protease, overview. For the synthesis position 74 is mutated to Lys in order to couple 7-methoxycoumarin-4-acetic acid, MCA, to the amine via an amide bond, in part to aid in the flexibility of the MCA to allow free rotation away from the active site and not affect binding and/or cleavage of the peptide. At position 77 the native Phe is replaced with the unnatural amino acid diaminopropionic acid to facilitate coupling of 2,4-dinitrophenyl to the peptide. Thr79 is mutated to a serine increasing kcat 2fold without affecting Km
-
-
?
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2 + H2O
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)L-NH2
-
i.e. peptide PL51, a SNAP-25-NH2in which all methionines were replaced by nonoxidizable Nle
-
-
?
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2 + H2O
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)L-NH2
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i.e. peptide PL50, a SNAP-25-NH2 acetylated at positions 156 to 203 [(pNO2-Phe)197, (1-pyrenylalanine)200, Nle202]
-
-
?
Ac-KSDSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)LGSG-NH2 + H2O
Ac-KSDSNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)LGSG-NH2
-
-
-
-
?
Ac-RGSNKPKIDAGNQRATRXLGGR-NH2 + H2O
Ac-RGSNKPKIDAGNQR + ATRXLGGR-NH2
-
-
-
?
Ac-SNKTIDEANQRATKML-NH2 + H2O
Ac-SNKTIDEANQ + RATKML-NH2
-
synaptosomal protein
-
?
Ac-SNKTRIDCANQRATKML-NH2 + H2O
Ac-SNKTRIDCANQ + RATKML-NH2
-
-
-
?
Ac-SNKTRIDEAN(1-pyrenylalanine)RA(pNO2-Phe)K(Nle)L-NH2 + H2O
Ac-SNKTRIDEAN(1-pyrenylalanine) + RA(pNO2-Phe)K(Nle)L-NH2
-
-
-
-
?
Ac-SNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2 + H2O
Ac-SNKTRIDEAN(pNO2-Phe) + RA(1-pyrenylalanine)K(Nle)L-NH2
-
-
-
-
?
Ac-SNKTRIDEANQRATK(Nle)L-NH2 + H2O
Ac-SNKTRIDEANQ + RATK(Nle)L-NH2
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-
-
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?
Ac-SNKTRIDEANQRATKML-NH2 + H2O
Ac-SNKTRIDEANQ + RATKML-NH2
-
-
-
?
Ac-SNKTRIDEANQRCTKML-NH2 + H2O
Ac-SNKTRIDEANQ + RCTKML-NH2
-
-
-
?
Ac-SNKTRIDECNQRATKML-NH2 + H2O
Ac-SNKTRIDECNQ + RATKML-NH2
-
-
-
?
biotin-KGSNRTRIDQGNQRATRXLGGK-biotin + H2O
?
-
the catalytic activity resides on the light chains of the toxin molecule
-
-
?
LQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDD + H2O
LQQTQAQVDEVVDI + MRVNVDKVLERDQK + LSELDD
-
the vesicle-associated membrane protein, VAMP, sequence-derived peptide is a substrate of BoNT serotype D light chain
-
-
?
LSELDDRADALQAGASQFETSAAKLKRKYWWKNLK + H2O
LSELDDRADALQAGASQ + FETSAAKLKRKYWWKNLK
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the vesicle-associated membrane protein, VAMP, sequence-derived peptide is a substrate of BoNT serotype B light chain
-
-
?
membrane-anchored SNARE + H2O
?
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host membrane-anchored SNARE, proteolytically cleaved by BoNT/C
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-
?
Nutide + H2O
?
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i.e. FITC(bA)T(dR)IDQANQRAT(K/DABCYL)(Nle)-amide
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?
Proteins of neuroexocytosis apparatus + H2O
?
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-
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?
Recombinant glutathione S-methyltransferase VAMP-2 fusion protein + H2O
Hydrolyzed recombinant glutathione S-methyltransferase VAMP-2 fusion protein
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2 proteolytic fragments, MW 36000 and MW 6000
?
Sb-Snc2p fusion protein + H2O
?
-
a recombinant chimeric SNARE protein where a portion of neuronal synaptobrevin, Sb, is fused to Snc2p, a Sb ortholog required for protein secretion from yeast cells
-
-
?
SNAP-23 + H2O
?
-
a nonneuronal SNARE protein, that mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. SNAP23 is cleaved by an engineered BoNT/E light chain, LC/E K224D. Molecular modeling of the enzyme-substrate complex using the crystal structure of LC/E, Protein Data Bank ID 3d3x, overview
-
-
?
SNAP-25 peptide (141-206) + H2O
?
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the minimal size of SNAP-25 known to retain full activity as a BoNT/A substrate is the C-terminal 66-mer peptide, residues 141-206, with both exosites
-
-
?
SNAP-25-derived peptide + H2O
?
-
i.e. HA-tagged SNAP25(141-206) or HA-tagged mutant SNAP25(141-206)-R198A, substrate of light chains of BoNT/A1, BoNT/A2, BoNT/A3, and BoNT/A4
-
-
?
SNAP25(187-203) + H2O
?
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i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, substrate fragmnent containing residues 87-203
-
-
?
SNAPEtide + H2O
?
substrate for subtype BoNT/E
-
-
?
SNARE-protein + H2O
?
-
soluble NSF-attachment protein receptor
-
?
SNKTRIDEAAQRATKML + H2O
SNKTRIDEAAQ + RATKML
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synthetic peptide substrate
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?
SNKTRIDEANBRATKML + H2O
SNKTRIDEANB + RATKML
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synthetic peptide substrate
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?
SNKTRIDEANNRATKML + H2O
SNKTRIDEANN + RATKML
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synthetic peptide substrate
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?
SNKTRIDEANQRABKML + H2O
SNKTRIDEANQ + RABKML
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synthetic peptide substrate
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?
SNKTRIDEANQRASKML + H2O
SNKTRIDEANQ + RASKML
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synthetic peptide substrate
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?
SNKTRIDEANQRATAML + H2O
SNKTRIDEANQ + RATAML
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synthetic peptide substrate
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?
SNKTRIDEANQRATK + H2O
SNKTRIDEANQ + RATK
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKAL + H2O
SNKTRIDEANQ + RATKAL
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKM + H2O
SNKTRIDEANQ + RATKM
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKXL + H2O
SNKTRIDEANQ + RATKXL
-
synthetic peptide substrate
-
?
SNKTRIDEANQRBTKML + H2O
SNKTRIDEANQ + RBTKML
-
synthetic peptide substrate
-
?
SNKTRIDEBNQRATKML + H2O
SNKTRIDEBNQ + RATKML
-
synthetic peptide substrate
-
?
SNKTRINEAAQRATKML + H2O
SNKTRINEAAQ + RATKML
-
synthetic peptide substrate
-
?
SNRTRIDEANK(Dnp)RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML + H2O
SNRTRIDEANK(Dnp) + RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML
synaptobrevin-2 + H2O
?
-
cleaves in the same location as that cleaved by BoNT/F proteolytic F toxin of Clostridium botulinum
-
-
?
Synaptosome-associated protein + H2O
?
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
synaptosome-associated protein SNAP-25 + H2O
hydrolyzed synaptosome-associated protein SNAP-25
-
-
-
-
?
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQKLSELDDRADAL + H2O
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ + KLSELDDRADAL
-
-
-
?
VAMP-1 + H2O
?
-
subtype BoNT/D does not cleave human VAMP-1 efficiently
-
-
?
VAMP2 peptide + H2O
?
-
a synthetic peptide substrate representing amino acid residues 60-94 of the intracellular vesicle associated membrane protein 2, i.e. VAMP2, recombinant GST fusion protein and commercial preparation as substrates with equal activity for BONT/B
-
-
?
vesicle-associated membrane protein VAMP + H2O
?
-
BoNT F cleaves VAMP between residues Q58 and K59. The minimum substrate is a peptide containing VAMP residues 32-65, which includes only one of the two VAMP structural motifs thought to be required for botulinum substrate recognition. BoNT F exhibits a strict requirement for residues D57 (P2), K59 (P1'), and L60 (P2'), but peptides containing substitutions for R56 (P3), Q58 (P1), and S61 (P3') are cleaved. Therefore, the P2, P1', and P2'?residues of VAMP are of paramount importance for BoNT F substrate recognition near the scissile bond
-
-
?
vesicle-associated membrane protein-2 mutant D51A + H2O
?
-
the enzyme cleaves the mutant substrate with about 10fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant E41A + H2O
?
-
the enzyme cleaves the mutant substrate with about 80fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant E55A + H2O
?
-
the enzyme cleaves the mutant substrate with about 750fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant K52A + H2O
?
-
the enzyme cleaves the mutant substrate with about 20fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant N49A + H2O
?
-
the enzyme cleaves the mutant substrate with about 10fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant Q58A + H2O
?
-
the enzyme cleaves the mutant substrate with about 25fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant R31A + H2O
?
-
the enzyme cleaves the mutant substrate with about 20fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant R56A + H2O
?
-
the enzyme cleaves the mutant substrate with about 4000fold lower efficiency compared to the wild type substrate
-
-
?
vesicle-associated membrane protein-2 mutant V50A + H2O
?
-
the enzyme cleaves the mutant substrate with about 50fold lower efficiency compared to the wild type substrate
-
-
?
cytosolic SNARE + H2O
?
-
host cytosolic SNARE, i.e. soluble NSF attachment protein receptor, a central helical protein-conducting channel, which chaperones the protease across host endosomes, modelling, overview. Sequence-specific claveage by the endoprotease activity of the BoNT light chains
-
-
?
cytosolic SNARE + H2O
?
-
host cytosolic SNARE, i.e. soluble NSF attachment protein receptor, a central helical protein-conducting channel, which chaperones the protease across host endosomes, modelling, overview. Sequence-specific claveage by the endosprotease activity of the BoNT light chains. Enzyme-substrate complex, overview
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
neurotoxin binds specifically to nerve cells, botulin neurotoxin-receptors are located on the motor neuron plasmalemma at neuromuscular junctions, neurotoxin binds via protein and lipid interaction, after binding it is internalized inside vesicles of unknown nature
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
involved in limited hydrolysis of proteins of the neuroexocytosis apparatus, blocks release of neurotransmitter acetylcholine at neuromuscular junction
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
causing flaccid paralysis, in contrast to spastic paralysis caused by EC 3.4.24.68, three functionally distinct domains: domain L blocks neuroexocytosis, domain HN governs cell penetration, domain HC responsible for neurospecific binding
-
-
?
SNAP-25 + H2O
?
-
-
-
-
?
SNAP-25 + H2O
?
P10845
BoNT/A-LC is a Zn(II)-dependent metalloprotease that blocks the release of acetylcholine at the neuromuscular junction by cleaving SNAP-25, one of the SNARE proteins required for exocytosis
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa
-
-
?
SNAP-25 + H2O
?
P10845
i.e. synaptosomal associated protein of 25 kDa
-
-
?
SNAP-25 + H2O
?
serotypes BoNT/A and BoNT/E cleave SNAP-25 at distinct sites, BoNT/E blocks neurotransmission faster and more potently
-
-
?
SNAP-25 + H2O
?
-
the potent botulinum neurotoxin inhibits neurotransmitter release at cholinergic nerve terminals, causing a descending flaccid paralysis characteristic of the disease botulism
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa, all botulinus neurotoxin serotypes cleave the substrate at a unique peptide bond, BoNT/A cleaves SNAP-25 between residues Gln197 and Arg198. Phe194, Ile161, and Asp370 form the S1' subsite responsible for binding the P1' arginine side chain of SNAP-25, overview
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa, human substrate, substrate peptide fragment products, overview
-
-
?
SNAP-25 + H2O
?
-
serotype BoNT/C1-LC exhibits dual specificity toward both syntaxin and SNAP-25, in contrast to other serotypes, due to a distinct pocket S1' near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin, activity of the serotype C enzyme BoNT/C1-LC with diverse SNAp-25 substrate mutants, overview
-
-
?
SNAP-25 + H2O
?
substrate is a recombinant GFP-SNAP-25-(134206)-His6 fusion protein
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, BoNT/A requires two extended exosites for optimal substrate binding and recognition of its intracellular target SNAP-25
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosomal-associated protein, substrate of BoNT/A
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein
-
-
?
SNAP-25 + H2O
?
P10845
i.e. 25-kDa synaptosome-associated protein
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, a substrate of BoNT/A light chain
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, BoNT/A
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, is involved in acetylcholine release at the neuromuscular junction
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, a plasma membrane-associated protein, proteolytically cleaved by BoNT types A, C, and E
-
-
?
SNAP-25 + H2O
?
-
a neuronal SNARE protein, cleaved by an engineered BoNT/E light chain, LC/E K224D
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosomal-associated protein, substrate of BoNT serotypes A and E
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, design and construction of a lab-on-a-chip for the in vitro detection of BoNT-A activity using an assay that measures cleavage of the fluorescence-labeled peptide substrate specific for BoNT-A by the toxin light chain, detection by Foerster resonance energy transfer, FRET, fluorescence, method development and evaluation, overview. The peptide substrate is labeled with internally labeled with the FRET pair fluorescein-thiocarbamoyl, FITC, and 4-(dimethyla-minoazo)benzene-4-carboxylic acid, DABCYL, or with FITC only for positive control
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, development of a BoNT/A-specific assay method, overview. Usage of BoNT/A cleavage-sensitive antibodies that only interact with full-length SNAP-25, the molecular target of the BoNT/A serotype. These antibodies exhibit high specificity for full-length SNAP-25, allowing the BoNT/A-mediated proteolysis of this protein to be measured in diverse assay formats, e.g. ELISA and immunofluorescent assay methods, detailed overview
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, substrate of light chains of BoNT/A1, BoNT/A2, BoNT/A3, and BoNT/A4
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, the Michaelis complex involves an extensive network of binding interactions ranging from the active site to the opposite surface of the BoNT/A. In the complex, the N-terminal residues of SNAP-25 147-167 form an alpha-helix, imbedded in the rear surface of BoNT/A while the C-terminal residues 201-204 form a distorted beta-strand, and the spanning residues are mostly extended
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, truncated version of SNAP-25
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein. The BoNT/E-truncated C-terminal peptide of SNAP-25 is CDMGNEIDTQNRQIDR
-
-
?
SNAP-25 + H2O
?
-
17-residue C-terminal peptide corresponding to residue 187-203 of SNAP-25
-
-
?
SNAP-25 + H2O
?
-
cleaved by the light chains of subtypes BoNT/A and BoNT/E
-
-
?
SNAP25 + H2O
?
-
i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, the enzyme cleaves SNARE proteins, i.e. SNAP receptor proteins, to elicit flaccid paralysis by inhibiting neurotransmitter-carrying vesicle fusion to the plasma membrane of peripheral neurons, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane, serotype E toxin cleaving SNAP25 prevents assembly of the synaptic fusion complex and therefore the fusion of the acetylcholine-containing vesicle and the synaptic membrane
-
-
?
SNAP25 + H2O
?
-
zinc-endopeptidase activity of the N-terminal light chain of BoNT/A on synaptosome-associated protein-25 kDa of the SNARE complex
-
-
?
SNAP25 + H2O
?
-
i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, recombinant GST-tagged wild-type and mutant D193A, R198A, R198E, and I171A substrates, full-length and truncated substrate, SNAP25 initially binds along the belt region of BoNT/A, which aligns the P5 residue to the S5 pocket at the periphery of the active site, binding site structures, reaction mechanism, molecular modeling of the LC/A active site domain, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosomal-associated protein of 25 kDa, SNAP25 with varying peptide length, substrate specificity of BoNT/C1, e.g. 17mer peptide corresponding to residues 187-203 of SNAP-25 is a substrate for BoNT/C1 (1-430), importance of remote exosites in BoNT/C1 required for activity, assay optimization, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane
-
-
?
SNAPtide + H2O
?
-
i.e. SNAPtide, as recombinant human SNAP25bHA protein expressed in Escherichia coli
-
-
?
SNKTRIDEANQRATKML + H2O
SNKTRIDEANQ + RATKML
-
synthetic peptide substrate
-
?
SNKTRIDEANQRATKML + H2O
SNKTRIDEANQ + RATKML
-
the SNAP-25 peptide is a BoNT serotype A light chain substrate, a 17-residue synthetic peptide corresponding to residues 187 to 203 of SNAP-25. Serotype C1 cleaves the serotype A substrate at a bond separated by only one residue compared to serotype A
-
-
?
SNRTRIDEANK(Dnp)RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML + H2O
SNRTRIDEANK(Dnp) + RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML
-
a SNAP-25 peptide, residues 187-203, substrate BoNT/A LC FRET-based assay
-
-
?
SNRTRIDEANK(Dnp)RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML + H2O
SNRTRIDEANK(Dnp) + RA(S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)-L-cysteine)RML
P10845
a synthetic fluorogenic peptide substrate of BoTxA/LC, representing amino acid residues 187-203 of SNAP25, a cleavage site of the enzyme
-
-
?
synaptobrevin + H2O
?
-
synaptic vesicle-associated membrane protein, neurotoxin responsible for human and animal botulism
-
-
?
synaptobrevin + H2O
?
-
a vesicle-associated membrane protein, also known as VAMP, the most abundant SV entity, proteolytically cleaved by BoNT types B, D, F, and G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
i.e. VAMP, neuronal vesicle-associated membrane protein, MW 19000, with 2 isoforms in human, chicken, in rat brain: synaptobrevin/VAMP-1 and synaptobrevin/VAMP-2, cleaves at Gln76-Phe77, the same site as botulin neurotoxin B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at -Asp-Gln-+-Lys-Leu-, serotype BoNT/G: cleavage at Ala83-Ala84 (VAMP-1), Ala81-Ala82 (VAMP-2)
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Gln76-Phe77
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Ala-+-Ala-Lys
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Gln-Lys-+-Leu-Ser
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
hydrolyzed by serotypes D, F or G
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
no substrate of serotype BoNT/A or E
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying synaptobrevin/VAMP-2
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
both isoforms are cleaved at the same rate
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
carrying Val76 instead of Gln76 is not hydrolyzed by serotype BoNT/B
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
highly specific neurotoxins
-
-
?
Synaptobrevin + H2O
Hydrolyzed synaptobrevin
-
serotype BoNT/B: cleavage at Ser-Gln-+-Phe-Glu (at the same site as the tetanus neurotoxin)
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
highly specific neurotoxins
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A and E
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro, in isolated synaptosomes
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asn-Gln-+-Arg-Ala
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/E: cleavage at Arg180-Ile181
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
no substrate of serotype BoNT/G
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
in vitro and in injected Aplysia neurons
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Asp-Arg-+-Ile-Met
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
native and recombinant protein
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
MW 25000
-
-
?
Synaptosome-associated protein + H2O
Hydrolyzed synaptosome-associated protein
-
serotype BoNT/A: cleavage at Gln197-Arg198
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
hydrolyzed by BoNT/A, BoNT/E and BoNT/CI
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
significant structural changes near the toxin's catalytic pocket upon substrate binding, probably serving to render the protease competent for catalysis
-
-
?
Syntaxin + H2O
?
-
in vitro, in synaptosomes and in injected Aplysia neurons
-
-
?
Syntaxin + H2O
?
-
serotype BoNT/C1-LC exhibits dual specificity toward both syntaxin and SNAP-25, in contrast to other serotypes, due to a distinct pocket S1' near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin
-
-
?
VAMP + H2O
?
-
i.e. vesicle associated membrane protein or synaptobrevin, BoNT/B, and BoNT/F
-
-
?
VAMP + H2O
?
i.e. vesicle-associated membrane protein/synaptobrevin
-
-
?
VAMP + H2O
?
-
i.e. vesicle-associated membrane protein/synaptobrevin, substrate of BoNT/B, /D, /F, /G, and /C
-
-
?
VAMP + H2O
?
-
i.e. neuronal vesicle-associated membrane protein, substrate of BoNT/B, /D, /F, and /G
-
-
?
VAMP + H2O
?
i.e. vesicle-associated membrane protein/synaptobrevin, activity with substrate fragments and mechanism of substrate recognition of BoNT F, overview. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis. In exosite 2, BoNT F Arg133 has a dominant role in allowing docking of the V1-SNARE motif, by interacting with the main chain of VAMP Val43, the side chain of VAMP Glu41 and with a water that interacts with other main chain residues of VAMP. The VAMP E41A mutant is 470% cleavage resistant, as compared to the native VAMP
-
-
?
VAMP 2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2
-
-
?
VAMP 2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2, with BoNT/B light chain
-
-
?
VAMP-2 + H2O
?
-
initial substrate recognition is mediated through sequential binding of VAMP-2 to the B1, B2 and B3 pockets in LC/F (light chain of BoNT serotype F), which directed VAMP-2 to the active site of LC/F and stabilized the active site substrate recognition, where the P2, P1' and P2' sites of VAMP-2 are specifically recognized by the S2, S1' and S2' pockets of LC/F to promote substrate hydrolysis
-
-
?
VAMP-2 + H2O
?
-
cleaved by the light chains of subtypes BoNT/B, BoNT/T, BoNT/D, and BoNT/F
-
-
?
VAMP2 + H2O
?
-
i.e. intracellular vesicle associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
human VAMP2 substrate, i.e. vesicle-associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
i.e. vesicle-associated membrane protein 2 or synaptobrevin-2, with BoNT/B light chain. BoNT/B HT exhibits little ability to cleave its substrate VAMP-2, when its LC and HC subunits are held together by a disulfide bond
-
-
?
VAMPTide + H2O
?
-
a VAMP-2-derived peptide substrate, modified with FRET, with BoNT/B light chain
-
-
?
vesicle-associated membrane protein-1 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-1 + H2O
?
the enzyme suybtype BoNT/X cleaves vesicle-associated membrane protein-1 with a 10times higher efficiency than subtype BoNT/B and tetanus neurotoxin
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
cleavage at Leu54-Glu55
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
cleavage between L54 and E55
-
-
?
vesicle-associated membrane protein-3 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-4 + H2O
?
cleavage at Lys87-Ser88
-
-
?
vesicle-associated membrane protein-5 + H2O
?
cleavage at Arg40-Ser41
-
-
?
additional information
?
-
-
catalytic activity requires reduction of the single interchain disulfide bond of the neurotoxin
-
-
?
additional information
?
-
-
catalytic activity requires reduction of the single interchain disulfide bond of the neurotoxin
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
no hydrolysis of short peptides spanning the respective cleavage sites of the target proteins
-
-
?
additional information
?
-
-
activating protease activity is localized on light or L-chain of neurotoxin
-
-
?
additional information
?
-
-
the clostridial neurotoxins differ from other proteases in the recognition of the tertiary structure of the target rather than the sequence of the peptide bond to be cleaved
-
-
?
additional information
?
-
-
neuroparalytic activity tested by intravenous injection into Balb/c mice
-
-
?
additional information
?
-
-
able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by flaccid paralysis
-
?
additional information
?
-
-
only mammalian proteins, SNAP-25 from Drosophila sp. and Torpedo sp. are no substrates
-
?
additional information
?
-
-
undergoes autocatalytic proteolytic processing and fragmentation
-
?
additional information
?
-
-
BoNTs are the most toxic proteins known with mouse LD50 values in the range of 1-5 ng/kg. They are responsible for the pathophysiology of botulism. BoNTs enter peripheral cholinergic nerve terminals, where they cleave one or two of the three core proteins of the neuroexocytosis apparatus and elicit persistent but reversible inhibition of neurotransmitter release
-
-
?
additional information
?
-
-
botulinum neurotoxins are a group of proteins produced by different strains of Clostridium botulinum, that are responsible for botulism disease
-
-
?
additional information
?
-
-
boutulinum neurotoxin is a potent inhibitor of neuroexocytosis. Organization and regulation of the neurotoxin gene. The botulinum neurotoxin and non-toxic protein genes are organized in two polycistronic operons transcribed in opposite orientation
-
-
?
additional information
?
-
-
BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs, soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors, which constitute part of the synaptic vesicle fusion machinery, botulinum neurotoxins cause the neuroparalytic syndrome of botulism, BoNTs are biological hazard to humans and a serious potential bioweapon threat with a lethal dose of 1 ng/kg body weight
-
-
?
additional information
?
-
-
clostridial neurotoxins are the causative agents of the neuroparalytic diseases botulism and tetanus blocking neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors, SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery
-
-
?
additional information
?
-
-
intraglandular injection of botulinum toxin leads to a transient denervation of the submandibular gland and this is associated with reduced salivary secretion in Wistar rats, which may be due to glandular denervation induced by the inhibition of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors involved in acetylcholine release at the neuroglandular junction and also specially inhibition of those involved in exocytosis of the granula of the acinar cells. Cell organelles and secretory granula show a clear atrophy of the acini, which is more prominent in glands injected with the combination of BoNT/A and B, overview
-
-
?
additional information
?
-
-
LC-mediated proteolysis of SNARE proteins and consequent inhibition of synaptic vesicle fusion to the presynaptic membrane of human motor neurons are responsible for flaccid paralysis associated with botulism
-
-
?
additional information
?
-
-
the cytopathic effect of C2I-C2IIa toxin, e.g. on human HeLa or colon cancer Caco-2 cells, or Vero cells, is higher for the single components compared to the complex
-
-
?
additional information
?
-
-
the enzyme causes neuroparalysis by blocking neurotransmitter release at the neuromuscular junctions
-
-
?
additional information
?
-
-
the neurotoxic enzyme causes the neuroparalytic illness botulism in humans acting as an endopeptidase which cleaves proteins that are necessary for acetylcholine exocytosis, botulinum toxin affets the strength-duration time constant in patients, the toxin acts on the Na+/K+ pump activity, overview
-
-
?
additional information
?
-
-
the proteolytically activated 60 kDa C2II binding component is essential for C2I transport into target cells involving especially amino acids Glu399, Asp426, and Phe428, it forms heptameric channels into membranes that are cation-selective and can be blocked by chloroquine and related compounds
-
-
?
additional information
?
-
P10845
the seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific SNARE complex proteins and block the release of neurotransmitters causing flaccid paralysis and are considered potential bioweapons, botulinum neurotoxin type A is the most potent among the clostridial neurotoxins
-
-
?
additional information
?
-
-
the seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific SNARE complex proteins and block the release of neurotransmitters causing flaccid paralysis and are considered potential bioweapons, botulinum neurotoxin type A is the most potent among the clostridial neurotoxins
-
-
?
additional information
?
-
the seven serotypes A-G potently block neurotransmission by binding to presynaptic receptors, undergoing endocytosis, transferring to the cytosol, and inactivating proteins essential for vesicle fusion, overview
-
-
?
additional information
?
-
-
toxicity in mice of full-length, single-nicked, and double-nicked enzyme forms, overview
-
-
?
additional information
?
-
-
development of a rapid assay method to distiguish the enzyme serotypes A, B, E, F, and G, substrate requirements of the different serotypes, overview
-
-
?
additional information
?
-
-
Glu224 and Glu262 are structurally essential for activity, structure-function relationship, overview
-
-
?
additional information
?
-
-
identification of active site and surrounding residues involved in substrate recognition and catalysis of BoNT/A, overview
-
-
?
additional information
?
-
-
LC-mediated proteolysis of soluble N-ethylmaleimide-sensitive factor attachment protein receptor, i.e. SNARE, proteins, complex reaction mechanism, overview
-
-
?
additional information
?
-
-
the catalytic component of the clostridial neurotoxins is their light chain, a Zn2+ endopeptidase, active site structure of serotype C1, substrate and cleavage site specificity of serotypes, overview
-
-
?
additional information
?
-
-
the enzyme is a binary toxin, which is composed of two separate proteins, the enzyme component C2I is an ADP-ribosyltransferase which modifies G-actin of eukaryotic cells, while the proteolytically activated binding/translocation component C2IIa forms ring-shaped heptamers, which bind to cell receptors and mediate the transport of C2I into the cytosol of target cells. Receptor-bound C2IIa serves as a docking platform for C2I on the cell surface, following assembly of C2I, the toxin complex is taken up via receptor-mediated endocytosis, and finally, C2IIa facilitates translocation of C2I from acidic endosomes into the cytosol, the preformed C2 toxin complex ADP-ribosylates actin in vitro and induces cell rounding, overview
-
-
?
additional information
?
-
-
the neurotoxin serotypes show distinct substrate specificities, overview
-
-
?
additional information
?
-
-
the the receptor-binding domain of botulinum neurotoxin serotype B binds to the luminal domain of synaptotagmin II, i.e. Syt-II, interaction occurs at both neutral and acidic endosomal pH, residues Glu44 to Lys60 become structured with residues Phe47 to Ile58 forming an alpha-helix, the HCB-Syt-II complex is stabilized by extensive intermolecular interactions involving two pronounced pockets on the HCB surface, structure, overview, high selectivity of BoNT/B among synaptotagmin I and II isoforms
-
-
?
additional information
?
-
BoNT E first binds to GT1b on the presynaptic membrane, like all other BoNTs. In BoNT B, the sialic acid of the sialyllactose that partly mimics GT1b binds in a shallow cavity formed by Trp1261 and His1240,12 and interacts with Tyr1262 and His1240, binding mode, overviewThe GT1b binding site in BoNT E is similar to those in other BoNTs and tetanus neurotoxin
-
-
?
additional information
?
-
-
BoNT E first binds to GT1b on the presynaptic membrane, like all other BoNTs. In BoNT B, the sialic acid of the sialyllactose that partly mimics GT1b binds in a shallow cavity formed by Trp1261 and His1240,12 and interacts with Tyr1262 and His1240, binding mode, overviewThe GT1b binding site in BoNT E is similar to those in other BoNTs and tetanus neurotoxin
-
-
?
additional information
?
-
-
BoNT serotypes bind to structure of ganglioside GT1b receptors, structure and binding specificities, modelling, overview
-
-
?
additional information
?
-
-
BoNT/A and BoNT/B bind a synaptic vesicle protein complex from synaptic vesicles, interactions of BoNT and host neuronal receptors, overview. Binding and entry of BoNTs at the neuromuscular junction, BoNT/A associates with the presynaptic membrane of alpha-motor neurons through interactions with oligosaccharides such as ganglioside GT1b, structure-function, modelling, overview
-
-
?
additional information
?
-
-
BoNT/A binds to peripheral cholinergic nerve terminals, causing their inhibition, rapidly and with high specificity via its receptor binding, heavy chain domain termed HC. BoNT/A interacts specifically with polysialogangliosides and with a luminal loop of the synaptic vesicle protein SV2 via the C-terminal half of HC, while the N-terminal half of it binds to sphingomyelin-enriched membrane microdomains and shows defined interaction with phosphatidylinositol phosphates, that might play a role in the correct positioning of the toxin for the subsequent low pH-driven membrane insertion of translocation domain sHN. Molecular modelling of Hc-N/A membrane binding, overview
-
-
?
additional information
?
-
BoNTs bind motor neurons via ganglioside-protein dual receptors, i.e. two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core, HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2, structure-function properties of BoNT/F host receptor interactions, dual receptors for BoNT/F, overview. Deglycosylation of glycoproteins disrupts the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, is unaffected. Mutations within the putative ganglioside binding pocket of HCR/F decrease binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons, overview
-
-
?
additional information
?
-
-
BoNTs exert their neurotoxic effect by a multistep mechanism: binding, internalization, membrane translocation, intracellular traffic, and proteolytic degradation of target. The protein receptors are SV2 for BoNT/A, BoNT/E, and BoNT/F, and synaptotagmin I and II for BoNT/B and BoNT/G. BoNTs enter sensitive host cells via receptor-mediated endocytosis, detailed overview. The protease is chaperoned across host endosomes, DELTApH of early endosomes is finely tuned to elicit drastic conformational changes, leading to the insertion of BoNT into the membrane, while it is auspiciously set to interrupt further processing in the harsh acidic conditions existent inside lysosomes. HC dictates the target cell specificity and, during cell binding and intracellular traffic, serves to chaperone the light chain and HN, which ensures that partial unfolding of the light chain is concomitant with HN channel formation, thereby promoting productive light chain translocation
-
-
?
additional information
?
-
botulinum neurotoxin binds host peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype. BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins, structure analysis of BoNT/G binding to Syt andGT1b, overview
-
-
?
additional information
?
-
-
design of BoNT A or B H-chain peptides for localizing BoNT/A binding regions to mouse brain synaptosomes
-
-
?
additional information
?
-
P10845
ganglioside GT1b is considered as BoNT/A receptor at nerve cells and can bind to the C-terminal end of the heavy chain
-
-
?
additional information
?
-
-
ganglioside GT1b is considered as BoNT/A receptor at nerve cells and can bind to the C-terminal end of the heavy chain
-
-
?
additional information
?
-
-
sialic acid-dependent binding is required for the transcytosis of serotype D botulinum neurotoxin and toxin complex L-TC in rat intestinal epithelial cell line IEC-6, mechanism, overview. HA-33 molecules play an important role in the effective binding of D-4947 L-TC to Caco-2 cells
-
-
?
additional information
?
-
-
the BoNT light chain domain is the Zn-dependent metalloprotease, that cleaves specific proteins that prevent acetylcholine release. BoNT shows endoproteolytic activity on one of the three SNARE proteins, i.e. soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins. The BoNT serotypes all show distinct cleavage sites on the SNARE substrates
-
-
?
additional information
?
-
-
the catalytic light chains of BoNTs, BoNT-LC, recognize extended regions of their substrates for cleavage
-
-
?
additional information
?
-
-
the heavy chain mediates the binding of the toxin with ganglioside and glycoprotein receptors at the neuronal surface, followed by toxin entry by means of receptor-mediated endocytosis. It mediates the translocation of the light chain into the neuronal cytosol, where it functions as a Zn2+-dependent endoprotease
-
-
?
additional information
?
-
-
the toxin light chain, LC, is a zinc-dependent endopeptidase that cleaves soluble N-ethylmaleimide-sensitive fusion proteins, SNARE, located at nerve endings
-
-
?
additional information
?
-
active site structure, Tyr351 is close to both nucleophilic water and catalytic zinc, overview
-
-
?
additional information
?
-
-
active site structure, Tyr351 is close to both nucleophilic water and catalytic zinc, overview
-
-
?
additional information
?
-
-
assay method measuring noradrenaline release in human neuronal SHSY-5Y cells
-
-
?
additional information
?
-
-
assay method measuring noradrenaline release in human neuronal SHSY-5Y cells
-
-
?
additional information
?
-
-
BoNT/E light chain mutant K224D does not cleave the SNARE proteins SNAP29 or SNAP47
-
-
?
additional information
?
-
-
development and evaluation of in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors, development of FRET substrates, overview
-
-
?
additional information
?
-
-
development of a fluorescence sandwich immunoassay for BoNT activity determination, using serotype BoNT/A, demonstration of its application in both 96-well plate- and bead-based assay formats, both involving a solid substrate, overview
-
-
?
additional information
?
-
-
development of an improved ultra-performance liquid chromatography product detection method, overview
-
-
?
additional information
?
-
-
development of Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A-G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples
-
-
?
additional information
?
-
-
development of internally quenched fluorescent substrates containing the fluorophore/repressor pair pyrenylalanine/4-nitrophenylalanine for a sensitive assay method. (pNO2-Phe) and (1-pyrenylalanine) are, respectively, introduced at positions 197 and 200 of the cleavable fragment, amino acids 187 to 203, of SNAP-25, with norleucine at position 202 [Nle202], which is acetylated at its N terminus and amidated at its C-terminus. Sensitivity is increased when the peptide sequence of the previous substrate is lengthened to account for exosite binding to BoNT/A, substrate specificity and assay optimization, overview
-
-
?
additional information
?
-
-
enzyme-substrate complex, detailed overview. BoNT/C is unique among the BoNTs, in that it cleaves both SNAP-25 and syntaxin, another plasma membrane-anchored SNARE
-
-
?
additional information
?
-
-
F1-40 is a mouse-derived, IgG1 monoclonal antibody that binds the light chain of BoNT serotype A and is used in a sensitive immunoassay for toxin detection, determination of binding epitopes, overview
-
-
?
additional information
?
-
-
feasibility of using the CFP-YFP pair with full-length SNAP-25 as a FRET-based substrate for BoNT/A in a cell-based assay or with the 66-mer peptide as a FRET substrate in an in vitro assay, optimization of FRET efficiency by use of fluorescent protein variants, CsY, CsYY or YsCsY, overview
-
-
?
additional information
?
-
-
functional assay of the toxin protease activity using a fluorogenic substrate. Development of a bead-based sandwich immunoassay for botulinum neurotoxin serotype A, BoNT/A, using a recombinant 50 kDa fragment of the BoNT/A heavy chain as a structurally valid simulant. Different anti-BoNT/A antibodies are attached to three different fluorescent, dye encoded flow cytometry beads for multiplexing. The assay is conducted in two formats: a manual microcentrifuge tube format and an automated fluidic system format. Flow cytometry detection is used for both formats, method evaluation, overview
-
-
?
additional information
?
-
-
recombinant BoNT/E fragment HC1163-1256 binds synaptotagmin and gangliosides, the expressed and purified HC1163-1256 protein retains a functionally active conformation
-
-
?
additional information
?
-
-
regions on BoNT/B that bind to blocking antibodies, synaptotagmin, or gangliosides, recognition pattern, overview
-
-
?
additional information
?
-
-
standard assay used to determine potency of clinical samples is the in vivo mouse bioassay, MBA, another possibilty is the primary rat spinal cord cells using RSC assay, that also permits sensitive and quantitative detection of BoNT/A, with usage of Sprague Dawley E15 rat pup spinal cords, Direct comparison of MBA and RSC assays, overview
-
-
?
additional information
?
-
-
substrate specificities of the BoNT light chain subtypes, overview. The LC subtypes perform autolytic cleavage. Each LC/A subtype possesses the di-tyrosine autocleavage site, which indicate that residues in addition to the cleavage site are necessary for autocleavage. Control LC, LC/A1 DYM, contains mutations to cleavage site residues, Y250A and Y251A, which abrogates autocatalysis in LC/A1
-
-
?
additional information
?
-
-
synaptosome capture assay for the different serotype BoNTs, synaptosome from rat brains, overview
-
-
?
additional information
?
-
-
usage of a single molecule assay of BoNT serotypes A and E light chain translocation through the heavy chain channel in neurons, and of BoNT intoxication assays, namely the mouse protection and the primary rat spinal cord cell assays
-
-
?
additional information
?
-
-
enzyme binding to the receptor synaptotagmin II is functionally related to the enzyme's toxic action
-
-
?
additional information
?
-
-
no activity with synaptosome-associated protein SNAP-25 and syntaxin
-
-
?
additional information
?
-
no activity with vesicle-associated membrane protein-7, vesicle-associated membrane protein-8, syntaxin 1, SNAP-25 and Sec22b
-
-
?
additional information
?
-
-
subtype BoNT/A6 enters cells more efficiently than other enzyme subtypes
-
-
?
additional information
?
-
-
the reduction of the disulfide bond is necessary for the optimum activity of the enzyme
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ac-SNKTIDEANQRATKML-NH2 + H2O
Ac-SNKTIDEANQ + RATKML-NH2
-
synaptosomal protein
-
?
cytosolic SNARE + H2O
?
-
host cytosolic SNARE, i.e. soluble NSF attachment protein receptor, a central helical protein-conducting channel, which chaperones the protease across host endosomes, modelling, overview. Sequence-specific claveage by the endoprotease activity of the BoNT light chains
-
-
?
membrane-anchored SNARE + H2O
?
-
host membrane-anchored SNARE, proteolytically cleaved by BoNT/C
-
-
?
SNARE-protein + H2O
?
-
soluble NSF-attachment protein receptor
-
?
Synaptosome-associated protein + H2O
?
-
i.e. SNAP 25, protein of presynaptic membrane
-
-
?
VAMP 2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
neurotoxin binds specifically to nerve cells, botulin neurotoxin-receptors are located on the motor neuron plasmalemma at neuromuscular junctions, neurotoxin binds via protein and lipid interaction, after binding it is internalized inside vesicles of unknown nature
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
involved in limited hydrolysis of proteins of the neuroexocytosis apparatus, blocks release of neurotransmitter acetylcholine at neuromuscular junction
-
-
?
Neuroexocytosis multi-subunit complex + H2O
?
-
causing flaccid paralysis, in contrast to spastic paralysis caused by EC 3.4.24.68, three functionally distinct domains: domain L blocks neuroexocytosis, domain HN governs cell penetration, domain HC responsible for neurospecific binding
-
-
?
SNAP-25 + H2O
?
P10845
BoNT/A-LC is a Zn(II)-dependent metalloprotease that blocks the release of acetylcholine at the neuromuscular junction by cleaving SNAP-25, one of the SNARE proteins required for exocytosis
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosomal associated protein of 25 kDa
-
-
?
SNAP-25 + H2O
?
serotypes BoNT/A and BoNT/E cleave SNAP-25 at distinct sites, BoNT/E blocks neurotransmission faster and more potently
-
-
?
SNAP-25 + H2O
?
-
the potent botulinum neurotoxin inhibits neurotransmitter release at cholinergic nerve terminals, causing a descending flaccid paralysis characteristic of the disease botulism
-
-
?
SNAP-25 + H2O
?
-
i.e. 25 kDa synaptosome-associated protein, BoNT/A requires two extended exosites for optimal substrate binding and recognition of its intracellular target SNAP-25
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosomal-associated protein, substrate of BoNT/A
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein
-
-
?
SNAP-25 + H2O
?
P10845
i.e. 25-kDa synaptosome-associated protein
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, a substrate of BoNT/A light chain
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, BoNT/A
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, is involved in acetylcholine release at the neuromuscular junction
-
-
?
SNAP-25 + H2O
?
-
i.e. 25-kDa synaptosome-associated protein, substrate of BoNT/A, /E, and /C
-
-
?
SNAP-25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, a plasma membrane-associated protein, proteolytically cleaved by BoNT types A, C, and E
-
-
?
SNAP25 + H2O
?
-
i.e. soluble N-ethylmaleimide-sensitive factor attachment protein 25, the enzyme cleaves SNARE proteins, i.e. SNAP receptor proteins, to elicit flaccid paralysis by inhibiting neurotransmitter-carrying vesicle fusion to the plasma membrane of peripheral neurons, overview
-
-
?
SNAP25 + H2O
?
-
i.e. synaptosome-associated protein of 25 kDa, located at the host synaptic membrane, serotype E toxin cleaving SNAP25 prevents assembly of the synaptic fusion complex and therefore the fusion of the acetylcholine-containing vesicle and the synaptic membrane
-
-
?
SNAP25 + H2O
?
-
zinc-endopeptidase activity of the N-terminal light chain of BoNT/A on synaptosome-associated protein-25 kDa of the SNARE complex
-
-
?
synaptobrevin + H2O
?
-
synaptic vesicle-associated membrane protein, neurotoxin responsible for human and animal botulism
-
-
?
synaptobrevin + H2O
?
-
a vesicle-associated membrane protein, also known as VAMP, the most abundant SV entity, proteolytically cleaved by BoNT types B, D, F, and G
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
-
-
?
synaptosome-associated protein SNAP-25 + H2O
?
-
botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates
-
-
?
VAMP + H2O
?
-
i.e. vesicle associated membrane protein or synaptobrevin, BoNT/B, and BoNT/F
-
-
?
VAMP + H2O
?
i.e. vesicle-associated membrane protein/synaptobrevin
-
-
?
VAMP + H2O
?
-
i.e. vesicle-associated membrane protein/synaptobrevin, substrate of BoNT/B, /D, /F, /G, and /C
-
-
?
VAMP2 + H2O
?
-
i.e. intracellular vesicle associated membrane protein 2
-
-
?
VAMP2 + H2O
?
-
i.e. synaptobrevin-2 or vesicle-associated membrane protein 2
-
-
?
vesicle-associated membrane protein-1 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-1 + H2O
?
the enzyme suybtype BoNT/X cleaves vesicle-associated membrane protein-1 with a 10times higher efficiency than subtype BoNT/B and tetanus neurotoxin
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-2 + H2O
?
cleavage at Gln58-Lys59
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
cleavage at Leu54-Glu55
-
-
?
vesicle-associated membrane protein-2 + H2O
?
-
cleavage between L54 and E55
-
-
?
vesicle-associated membrane protein-3 + H2O
?
cleavage at Arg66-Ala67
-
-
?
vesicle-associated membrane protein-4 + H2O
?
cleavage at Lys87-Ser88
-
-
?
vesicle-associated membrane protein-5 + H2O
?
cleavage at Arg40-Ser41
-
-
?
additional information
?
-
-
able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by flaccid paralysis
-
?
additional information
?
-
-
only mammalian proteins, SNAP-25 from Drosophila sp. and Torpedo sp. are no substrates
-
?
additional information
?
-
-
undergoes autocatalytic proteolytic processing and fragmentation
-
?
additional information
?
-
-
BoNTs are the most toxic proteins known with mouse LD50 values in the range of 1-5 ng/kg. They are responsible for the pathophysiology of botulism. BoNTs enter peripheral cholinergic nerve terminals, where they cleave one or two of the three core proteins of the neuroexocytosis apparatus and elicit persistent but reversible inhibition of neurotransmitter release
-
-
?
additional information
?
-
-
botulinum neurotoxins are a group of proteins produced by different strains of Clostridium botulinum, that are responsible for botulism disease
-
-
?
additional information
?
-
-
boutulinum neurotoxin is a potent inhibitor of neuroexocytosis. Organization and regulation of the neurotoxin gene. The botulinum neurotoxin and non-toxic protein genes are organized in two polycistronic operons transcribed in opposite orientation
-
-
?
additional information
?
-
-
BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs, soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors, which constitute part of the synaptic vesicle fusion machinery, botulinum neurotoxins cause the neuroparalytic syndrome of botulism, BoNTs are biological hazard to humans and a serious potential bioweapon threat with a lethal dose of 1 ng/kg body weight
-
-
?
additional information
?
-
-
clostridial neurotoxins are the causative agents of the neuroparalytic diseases botulism and tetanus blocking neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors, SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery
-
-
?
additional information
?
-
-
intraglandular injection of botulinum toxin leads to a transient denervation of the submandibular gland and this is associated with reduced salivary secretion in Wistar rats, which may be due to glandular denervation induced by the inhibition of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors involved in acetylcholine release at the neuroglandular junction and also specially inhibition of those involved in exocytosis of the granula of the acinar cells. Cell organelles and secretory granula show a clear atrophy of the acini, which is more prominent in glands injected with the combination of BoNT/A and B, overview
-
-
?
additional information
?
-
-
LC-mediated proteolysis of SNARE proteins and consequent inhibition of synaptic vesicle fusion to the presynaptic membrane of human motor neurons are responsible for flaccid paralysis associated with botulism
-
-
?
additional information
?
-
-
the cytopathic effect of C2I-C2IIa toxin, e.g. on human HeLa or colon cancer Caco-2 cells, or Vero cells, is higher for the single components compared to the complex
-
-
?
additional information
?
-
-
the enzyme causes neuroparalysis by blocking neurotransmitter release at the neuromuscular junctions
-
-
?
additional information
?
-
-
the neurotoxic enzyme causes the neuroparalytic illness botulism in humans acting as an endopeptidase which cleaves proteins that are necessary for acetylcholine exocytosis, botulinum toxin affets the strength-duration time constant in patients, the toxin acts on the Na+/K+ pump activity, overview
-
-
?
additional information
?
-
-
the proteolytically activated 60 kDa C2II binding component is essential for C2I transport into target cells involving especially amino acids Glu399, Asp426, and Phe428, it forms heptameric channels into membranes that are cation-selective and can be blocked by chloroquine and related compounds
-
-
?
additional information
?
-
P10845
the seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific SNARE complex proteins and block the release of neurotransmitters causing flaccid paralysis and are considered potential bioweapons, botulinum neurotoxin type A is the most potent among the clostridial neurotoxins
-
-
?
additional information
?
-
-
the seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific SNARE complex proteins and block the release of neurotransmitters causing flaccid paralysis and are considered potential bioweapons, botulinum neurotoxin type A is the most potent among the clostridial neurotoxins
-
-
?
additional information
?
-
the seven serotypes A-G potently block neurotransmission by binding to presynaptic receptors, undergoing endocytosis, transferring to the cytosol, and inactivating proteins essential for vesicle fusion, overview
-
-
?
additional information
?
-
-
toxicity in mice of full-length, single-nicked, and double-nicked enzyme forms, overview
-
-
?
additional information
?
-
BoNT E first binds to GT1b on the presynaptic membrane, like all other BoNTs. In BoNT B, the sialic acid of the sialyllactose that partly mimics GT1b binds in a shallow cavity formed by Trp1261 and His1240,12 and interacts with Tyr1262 and His1240, binding mode, overviewThe GT1b binding site in BoNT E is similar to those in other BoNTs and tetanus neurotoxin
-
-
?
additional information
?
-
-
BoNT E first binds to GT1b on the presynaptic membrane, like all other BoNTs. In BoNT B, the sialic acid of the sialyllactose that partly mimics GT1b binds in a shallow cavity formed by Trp1261 and His1240,12 and interacts with Tyr1262 and His1240, binding mode, overviewThe GT1b binding site in BoNT E is similar to those in other BoNTs and tetanus neurotoxin
-
-
?
additional information
?
-
-
BoNT serotypes bind to structure of ganglioside GT1b receptors, structure and binding specificities, modelling, overview
-
-
?
additional information
?
-
-
BoNT/A and BoNT/B bind a synaptic vesicle protein complex from synaptic vesicles, interactions of BoNT and host neuronal receptors, overview. Binding and entry of BoNTs at the neuromuscular junction, BoNT/A associates with the presynaptic membrane of alpha-motor neurons through interactions with oligosaccharides such as ganglioside GT1b, structure-function, modelling, overview
-
-
?
additional information
?
-
-
BoNT/A binds to peripheral cholinergic nerve terminals, causing their inhibition, rapidly and with high specificity via its receptor binding, heavy chain domain termed HC. BoNT/A interacts specifically with polysialogangliosides and with a luminal loop of the synaptic vesicle protein SV2 via the C-terminal half of HC, while the N-terminal half of it binds to sphingomyelin-enriched membrane microdomains and shows defined interaction with phosphatidylinositol phosphates, that might play a role in the correct positioning of the toxin for the subsequent low pH-driven membrane insertion of translocation domain sHN. Molecular modelling of Hc-N/A membrane binding, overview
-
-
?
additional information
?
-
BoNTs bind motor neurons via ganglioside-protein dual receptors, i.e. two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core, HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2, structure-function properties of BoNT/F host receptor interactions, dual receptors for BoNT/F, overview. Deglycosylation of glycoproteins disrupts the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, is unaffected. Mutations within the putative ganglioside binding pocket of HCR/F decrease binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons, overview
-
-
?
additional information
?
-
-
BoNTs exert their neurotoxic effect by a multistep mechanism: binding, internalization, membrane translocation, intracellular traffic, and proteolytic degradation of target. The protein receptors are SV2 for BoNT/A, BoNT/E, and BoNT/F, and synaptotagmin I and II for BoNT/B and BoNT/G. BoNTs enter sensitive host cells via receptor-mediated endocytosis, detailed overview. The protease is chaperoned across host endosomes, DELTApH of early endosomes is finely tuned to elicit drastic conformational changes, leading to the insertion of BoNT into the membrane, while it is auspiciously set to interrupt further processing in the harsh acidic conditions existent inside lysosomes. HC dictates the target cell specificity and, during cell binding and intracellular traffic, serves to chaperone the light chain and HN, which ensures that partial unfolding of the light chain is concomitant with HN channel formation, thereby promoting productive light chain translocation
-
-
?
additional information
?
-
botulinum neurotoxin binds host peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype. BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins, structure analysis of BoNT/G binding to Syt andGT1b, overview
-
-
?
additional information
?
-
-
design of BoNT A or B H-chain peptides for localizing BoNT/A binding regions to mouse brain synaptosomes
-
-
?
additional information
?
-
P10845
ganglioside GT1b is considered as BoNT/A receptor at nerve cells and can bind to the C-terminal end of the heavy chain
-
-
?
additional information
?
-
-
ganglioside GT1b is considered as BoNT/A receptor at nerve cells and can bind to the C-terminal end of the heavy chain
-
-
?
additional information
?
-
-
sialic acid-dependent binding is required for the transcytosis of serotype D botulinum neurotoxin and toxin complex L-TC in rat intestinal epithelial cell line IEC-6, mechanism, overview. HA-33 molecules play an important role in the effective binding of D-4947 L-TC to Caco-2 cells
-
-
?
additional information
?
-
-
the BoNT light chain domain is the Zn-dependent metalloprotease, that cleaves specific proteins that prevent acetylcholine release. BoNT shows endoproteolytic activity on one of the three SNARE proteins, i.e. soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins. The BoNT serotypes all show distinct cleavage sites on the SNARE substrates
-
-
?
additional information
?
-
-
the catalytic light chains of BoNTs, BoNT-LC, recognize extended regions of their substrates for cleavage
-
-
?
additional information
?
-
-
the heavy chain mediates the binding of the toxin with ganglioside and glycoprotein receptors at the neuronal surface, followed by toxin entry by means of receptor-mediated endocytosis. It mediates the translocation of the light chain into the neuronal cytosol, where it functions as a Zn2+-dependent endoprotease
-
-
?
additional information
?
-
-
the toxin light chain, LC, is a zinc-dependent endopeptidase that cleaves soluble N-ethylmaleimide-sensitive fusion proteins, SNARE, located at nerve endings
-
-
?
additional information
?
-
-
enzyme binding to the receptor synaptotagmin II is functionally related to the enzyme's toxic action
-
-
?
additional information
?
-
-
no activity with synaptosome-associated protein SNAP-25 and syntaxin
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zinc
Zn2+
additional information
Zinc
-
activation requires reduction of interchain disulfide bond
Zinc
-
contains zinc binding motif of metalloendopeptidases His-Glu-X-X-His
Zinc
-
contains zinc binding motif of metalloendopeptidases His223-Glu-Leu-Ile-His-X-X-His230
Zinc
-
1 atom of zinc per molecule botulinum neurotoxin, bound to light chain (i.e. L-chain)
Zinc
-
1 atom of zinc per molecule botulinum neurotoxin (MW 150000, of serotypes A, B and E, each in 2-chain form)
Zn2+
-
zinc endopeptidase, Zn2+ is the natural cofactor of the light chain
Zn2+
-
a zinc endopeptidase with a active site zinc binding motif HEXXH containing His223, His227, Glu224, and Glu262, structure, overview, thw zinc ion might play a structural role in addition to its catalytic role, overview
Zn2+
-
binding site structure, a long a helix contains the HEXXH Zn(II)-binding motif, modeling, overview
Zn2+
P10845
BoNT/A-LC is a Zn(II)-dependent metalloprotease, the Zn2+ ion plays a purely catalytic role
Zn2+
-
the catalytic component of the clostridial neurotoxins is their light chain, a Zn2+ endopeptidase
Zn2+
-
zinc endopeptidase, dependent on, addition of ZnCl2 to the assay mixture reduces the activity of BoNT/A, activity ratio of wild-type and mutant enzymes in presence or absence of ZnCl2, overview, BoNT/A LC undergoes autocatalytic degradation into two major fragments in the presence of exogenous zinc
Zn2+
the active-site zinc is coordinated by His212, His216, and Glu251, and nucleophilic water, which in turn is hydrogen-bonded to Glu213. Tyr351 is close to both nucleophilic water and catalytic zinc
Zn2+
-
the N-terminal A domain, i.e. light chain, LC, is a 50 kDa zinc metalloprotease with the characteristic thermolysin-family zinc coordination motif HExxH
Zn2+
-
the zinc ion in the active site is purely catalytic, the light chain module is a Zn2+-metalloprotease with a thermolysin-like fold
additional information
-
no involvement of cobalt, copper, iron, manganese or nickel, atomic absorption spectroscopy
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
toosendanin
an enzyme translocation inhibitor that hinders subtype BoNT/B oligomerization
(2E)-2-(1H-benzimidazol-2-yl)-3-(3-iodo-4-methoxyphenyl)prop-2-enenitrile
-
-
(2E)-3-(4-chlorophenyl)-N-hydroxyprop-2-enamide
-
a trans-cinnamic hydroxamate
(2E)-3-[4-chloro-2-(trifluoromethyl)phenyl]-N-hydroxyprop-2-enamide
-
-
(2E)-4-[(7-nitro-9H-fluoren-2-yl)amino]-4-oxobut-2-enoic acid
-
19.5% inhibition at 0.02 mM
(3alpha,5beta,7alpha,12alpha,17alpha)-24-([2-[(7-chloroquinolin-4-yl)amino]ethyl]amino)cholane-3,7,12-triyl triacetate
P10845
90% inhibition at 0.02 mM
([[5-[[1-(4-ammoniobutyl)-2-phenyl-1H-indol-6-yl]carbonyl]-2-(3-hydroxyphenyl)thiophen-3-yl]acetyl]amino)oxidanide
-
synthesis and binding structure, overview, multiple molecular dynamics simulations of the endopeptidase in complex with inhibitor 2 using the dummy atom approach, overview
1-(2,4-dichlorobenzyl)-1H-pyrrole-2,5-dione
-
inhibitor is providing relatively potent BoNT protection in a cellular assay. It inhibits the biological activity of BoNT/A1 in neuronal cells. This inhibitor is about 7 to 10times more potent than 2-(2,4-dichlorobenzylidene)cyclopent-4-ene-1,3-dione
2'-((9H-fluoren-2-ylamino)carbonyl)-4,4'-bis(hydroxy(oxido)amino)[1,1'-biphenyl]-2-carboxylic acid
-
82% inhibition at 0.02 mM
2'-[(7-fluoro-9H-fluoren-2-yl)carbamoyl][1,1'-biphenyl]-2-carboxylic acid
-
47.6% inhibition at 0.02 mM
2'-[(7-methoxy-9H-fluoren-2-yl)carbamoyl]biphenyl-2-carboxylic acid
-
20.9% inhibition at 0.02 mM
2'-[(9-hydroxy-9H-fluoren-2-yl)carbamoyl]biphenyl-2-carboxylic acid
-
20% inhibition at 0.02 mM
2'-[(9-oxo-9H-fluoren-2-yl)carbamoyl][1,1'-biphenyl]-2-carboxylic acid
-
20.2% inhibition at 0.02 mM
2'-[(9H-fluoren-2-yl)carbamoyl][1,1'-biphenyl]-2-carboxylic acid
-
37.2% inhibition at 0.02 mM
2,2'-(1,4-dioxobutane-1,4-diyl)dibenzoic acid
-
21.2% inhibition at 0.02 mM
2,4-dichlorocinnamic hydroxamate
-
binding site and complex structure, overview
2-(1,2-dihydroacenaphthylene-5-carbonyl)benzoic acid
-
11.5% inhibition at 0.02 mM
2-(1H-benzo[d]imidazol-2-yl)-3-(5-(furan-2-yl)thiophen-2-yl)acrylonitrile
-
-
2-(2,3-dihydro-1H-indene-5-carbonyl)benzoic acid
-
16.3% inhibition at 0.02 mM
2-(2,4-dichlorobenzylidene)cyclopent-4-ene-1,3-dione
-
inhibits the biological activity of BoNT/A1 in neuronal cells. This inhibitor is about 7 to 10times less potent than 1-(2,4-dichlorobenzyl)-1H-pyrrole-2,5-dione
2-(2-oxo-2,3-dihydro-1,3-benzoxazole-5-carbonyl)benzoic acid
-
35% inhibition at 0.02 mM
2-(3,5-dichloro-2-hydroxybenzoyl)benzoic acid
-
19.2% inhibition at 0.02 mM
2-(3-methyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoic acid
-
24.8% inhibition at 0.02 mM
2-(4-(2,4-dichlorophenoxy)phenyl)-6-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole
-
-
2-(4-(2-chloro-4-cyanophenoxy)phenyl)-6-(4,5-dihydro-1H-imidazol-2-yl)indole
-
-
2-(4-(4-(6-(1,4,5,6-tetrahydropyrimidin-2-yl)benzo[b]thiophen-2-yl)phenoxy)phenyl)-1,4,5,6-tetrahydropyrimidine
-
-
2-(4-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzo[b]thiophen-2-yl)phenoxy)phenyl)-4,5-dihydro-1H-imidazole
-
-
2-(4-(4-(6-(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)-1H-indol-2-yl)phenoxy)phenyl)-1,4,5,6-tetrahydropyrimidin-5-ol
-
-
2-(4-(6-(1,4,5,6-tetrahydropyrimidin-2-yl)benzo[b]thiophen-2-yl)phenyl)-1,4,5,6-tetrahydropyrimidine
-
-
2-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzo[b]thiophen-2-yl)-phenyl)-4,5-dihydro-1H-imidazole
-
-
2-(5-{[1-(4-aminobutyl)-2-phenyl-1H-indol-6-yl]carbonyl}-2-phenylthiophen-3-yl)-N-hydroxyacetamide
-
i.e. 2-(5-[[1-(4-aminobutyl)-2-phenyl-1H-indol-6-yl]carbonyl]-2-phenylthiophen-3-yl)-N-hydroxyacetamide
2-([1,1'-biphenyl]-4-carbonyl)benzoic acid
-
37.8% inhibition at 0.02 mM
2-[(3-bromo-9-oxo-9H-fluoren-2-yl)carbamoyl]cyclohexane-1-carboxylic acid
-
19.3% inhibition at 0.02 mM
2-[(4-bromo-9-oxo-9H-fluoren-2-yl)carbamoyl]benzoic acid
-
26.2% inhibition at 0.02 mM
2-[(9-oxo-9H-fluoren-2-yl)carbamoyl]benzoic acid
-
14.8% inhibition at 0.02 mM
2-[(9-oxo-9H-fluoren-2-yl)carbamoyl]cyclohexane-1-carboxylic acid
-
18.3% inhibition at 0.02 mM
2-[(9H-fluoren-2-yl)carbamoyl]cyclohexane-1-carboxylic acid
-
12% inhibition at 0.02 mM
-
2-[1-cyano-2-(3-bromo-5-methoxy-4-hydroxyphenyl)vinyl]benzimidazole
-
-
2-[1-cyano-2-(3-chloro-5-methoxy-4-hydroxyphenyl)vinyl]benzimidazole
-
-
2-[4-(methylamino)-3-nitrobenzoyl]benzoic acid
-
14.1% inhibition at 0.02 mM
2-[5-{[1-(4-aminobutyl)-2-phenyl-1H-indol-6-yl]carbonyl}-2-(3-hydroxyphenyl)thiophen-3-yl]-N-hydroxyacetamide
-
i.e. 2-[5-[[1-(4-aminobutyl)-2-phenyl-1H-indol-6-yl]carbonyl]-2-(3-hydroxyphenyl)thiophen-3-yl]-N-hydroxyacetamide, 79% inhibition of BoNTA at 0.02 mM
2-[5-{[1-(4-aminobutyl)-3-fluoro-2-phenyl-1H-indol-6-yl]carbonyl}-2-(3-aminophenyl)thiophen-3-yl]-N-hydroxyacetamide
-
i.e. 2-(5-(1-(4-aminobutyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)-2-(3-aminophenyl)thiophen-3-yl)-N-hydroxyacetamide, 47% inhibition of BoNTA at 0.02 mM. The hydroxamate coordinates the zinc ion embedded in the active site and forms a hydrogen bond to Glu224. The cation shows pi-interaction of the thiophene-substituted phenyl group with Arg363. Occurence of pi-pi interactions of the thiophene-substituted phenyl group with Phe194 and Tyr366, of interaction of the ketone oxygen atom with Asp370 that is bridged by at least one water molecule, and of cation-pi and pi-pi interactions of the indole-substituted phenyl group with Lys66 and Gln162, respectively
2-[5-{[1-(4-aminobutyl)-3-fluoro-2-phenyl-1H-indol-6-yl]carbonyl}-2-(4-hydroxyphenyl)thiophen-3-yl]-N-hydroxyacetamide
-
i.e. 2-(5-(1-(4-aminobutyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)-2-(4-hydroxyphenyl)thiophen-3-yl)-N-hydroxyacetamide, 82% inhibition of BoNTA at 0.02 mM. The hydroxamate coordinates the zinc ion embedded in the active site and forms a hydrogen bond to Glu224. The cation shows pi-interaction of the thiophene-substituted phenyl group with Arg363. Occurence of pi-pi interactions of the thiophene-substituted phenyl group with Phe194 and Tyr366, of interaction of the ketone oxygen atom with Asp370 that is bridged by at least one water molecule, and of cation-pi and pi-pi interactions of the indole-substituted phenyl group with Lys66 and Gln162, respectively
2-[[17-oxoestra-1,3,5(10)-trien-3-yl]oxy]cyclohexa-2,5-diene-1,4-dione
A5HZZ9
-
24-mer C-terminal peptide of LcE1
-
the activity of the light chain of botulinum toxin A is significantly reduced to 32% by the peptide with sequence TGRGLVKKIIRFCKNIVSVKGIRK
-
3,9-dichloro-6-(5,7-dichloro-9H-fluoren-2-yl)-5H-dibenzo[c,e]azepine-5,7(6H)-dione
-
68.9% inhibition at 0.02 mM
3,9-dichloro-6-(9H-fluoren-2-yl)-5H-dibenzo[c,e]azepine-5,7(6H)-dione
-
48% inhibition at 0.02 mM
3-(2,4-dichlorophenyl)-5-(4-fluorophenethoxy)-N-hydroxypentanamide
A5HZZ9
-
3-(2,4-dichlorophenyl)-N1-(4-fluoro-2-methoxyphenyl)-N5-hydroxypentanediamide
A5HZZ9
-
3-(2,4-dichlorophenyl)-N1-(4-fluorophenethyl)-N5-hydroxypentanediamide
A5HZZ9
-
3-(2,4-dichlorophenyl)-N1-hydroxy-N5-(4-methoxyphenethyl)pentanediamide
A5HZZ9
-
3-(4-(1H-imidazol-1-yl)phenyl)-2-(1H-benzoimidazol-2-yl)acrylonitrile
-
-
3-fluoro-2-(naphthalene-2-carbonyl)benzoic acid
-
43.9% inhibition at 0.02 mM
3-hydroxy-N'-[(E)-(2-hydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
A5HZZ9
-
3-hydroxy-N'-[(E)-(3,4,5-trihydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
A5HZZ9
competitive inhibition
3-hydroxy-N'-[(E)-(3-hydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
A5HZZ9
-
3-hydroxy-N-phenylanthracene-2-carboxamide
-
70.1% inhibition at 0.02 mM
32-mer C-terminal peptide of LcA
-
the activity of the light chain of botulinum toxin A is significantly reduced to 15% by the peptide with sequence KNFTGLFEFYKLLCVRGIITSKTKSLDKGYNK
-
4,4'-dichloro-2'-((9H -fluoren-2-ylamino)carbonyl)[1,1'-biphenyl]-2-carboxylic acid
-
88.3% inhibition at 0.02 mM
4,4'-dichloro-2'-[(5,7-dichloro-9H-fluoren-2-yl)carbamoyl][1,1'-biphenyl]-2-carboxylic acid
-
79.11% inhibition at 0.02 mM
4-chloro-(3-fluorophenyl)methyl benzenesulfonamide
-
i.e. MSU84, competitive inhibitor of botulinum neurotoxin type A light chain
4-chloro-N-[(4-fluorophenyl)methyl] pyridin-3-amine
-
i.e. MSU58, competitive inhibitor of botulinum neurotoxin type A light chain
4-[((2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2R)-2-phenylethylcarbamoyl)-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl)]benzoic acid
-
-
4-[((2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-(4-hydroxyphenyl)ethylcarbamoyl)-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl)]benzoic acid
-
-
4-[((2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1H-indol-3-yl)ethylcarbamoyl]-3(S)sulfanylpropyl)]benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-(3H-imidazol-4-yl)ethylcarbamoyl]-(2S)-2-biphenyl-4-ylethylcarbamoyl)-3(S)sulfanylpropyl]benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-methylbutylcarbamoyl)-(2S)-2-biphenyl-4-ylethylcarbamoyl]-3(S)-sulfanylpropyl]benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2R)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl]benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1-methyl-1H-indol-3-yl)ethylcarbamoyl]-3(S)sulfanylpropyl] benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-naphthalen-1-yl-ethylcarbamoyl]-3(S)sulfanylpropyl] benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl]-3(S)sulfanylpropyl)] benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(2S)-2-benzol[beta]thiophen-3-yl-1-benzylcarbamoylethylcarbamoyl-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3-(S)-sulfanylpropyl] benzoic acid
-
-
4-[(2S)-2-amino-3-[1-(2S)-2-benzo[b]thiophen-3-yl-1-benzylcarbamoylethylcarbamoyl-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)-sulfanylpropyl]benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2R)-2-phenylethylcarbamoyl)-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-(3H-imidazol-4-yl)ethylcarbamoyl]-(2S)-2-biphenyl-4-yl-ethylcarbamoyl}-3(S)sulfanylpropyl)}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-(4-hydroxyphenyl)ethylcarbamoyl)-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2R)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1-methyl-1H-indol-3-yl)ethylcarbamoyl]-3(S)sulfanylpropyl}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1H-indol-3-yl)ethylcarbamoyl]-3(S)sulfanylpropyl}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-naphthalen-1-yl-ethylcarbamoyl]-3(S)sulfanylpropyl}benzoic acid
-
-
4-{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl]-3(S)-sulfanylpropyl)}benzoic acid
-
-
5-((3-bromoadamantan-1-yl)methoxy)-3-(2,4-dichlorophenyl)-N-hydroxypentanamide
A5HZZ9
-
5-chloro-7-[(2,4-difluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(2,4-difluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(2,4-difluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(2-fluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(2-fluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(2-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(4-fluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(4-fluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
-
-
5-chloro-7-[(4-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
-
-
6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-(4-(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-(4-(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)phenyl)-1H-indole
-
-
6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-{5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]pyridin-2-yl}-1H-indole
-
-
6-(3,4,5,6-tetrahydropyrimidin-2-yl)-2-(4-(3,4,5,6-tetrahydropyrimidin-2-yl)phenyl)-1H-indole
-
-
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-1H-indole
-
-
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)phenyl)-1H-indole
-
-
6-(4,5-dihydroimidazol-2-yl)-2-(5-(4-(4,5-dihydroimidazol-2-yl)phenoxy)pyridine-2-yl)indole
-
-
6-(9H-fluoren-2-yl)-3,9-dinitro-5H-dibenzo[c,e]azepine-5,7(6H)-dione
-
24.7% inhibition at 0.02 mM
6-chloro-2-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)-phenyl)-1H-indole
-
-
6-[(2,5-dimethoxyphenyl)amino]-N-(4-phenoxybenzyl)picolinamide
A5HZZ9
-
6-[(3,6-dioxocyclohexa-1,4-dien-1-yl)amino]-N-(4-phenoxybenzyl)picolinamide
A5HZZ9
-
7-[(2,4-difluorophenyl)[(pyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(2,4-difluorophenyl)[(pyridin-3-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(2,4-difluorophenyl)[(pyrimidin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(2-fluorophenyl)[(pyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(2-fluorophenyl)[(pyridin-3-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(2-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(4-fluorophenyl)[(pyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(4-fluorophenyl)[(pyridin-3-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
7-[(4-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
Ala-Ser-Gln-Phe-Glu-Thr-Ser
-
synthetic peptide containing cleavage site of synaptobrevin, inhibits toxin action on buccal ganglion of Aplysia californica, serotype BoNT/B, not A or E
ammonium chloride
-
affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis
antibody F1-40
-
F1-40 binds a peptide fragment of the BoNT/A light chain, designated L1-3, which spans from T125 to L200, with recognition motif QPDRS. No binding to BoNT/A mutant Q138G/P139G/D140G. Wild-type residues Q138, P139 and D140 form a loop on the external surface of BoNT/A, exposed to solvent
-
AQVDEVVDIMRVNVDKVLERDQ
-
residues 37-58 of vesicle-associated membrane protein VAMP. Inhibitor exhibits a high degree of specificity for BoNT F, compared to other BoNT serotypes
bafilomycin A1
-
inhibits all BoNT serotypes. The ATPase inhibitor also functions as antagonist of the acidification process
buforin I
-
natural peptide, isolated from the stomach of the Asian toad Bufo bufo gargarizans
-
CB 7969312
-
the quinolinol-based analogue effectively neutralizes BoNT/A toxicity, ex vivo protection at 500 nM
CpA
-
i.e. [5-(4-chlorobenzoyl)-2-phenylthiophen-3-yl]acetic acid, 15% inhibition of BoNTA at 0.1 mM
D-chicoric acid
-
mechanism of inhibition, overview. The inhibitor binds to an exosite, displays noncompetitive partial inhibition, and is synergistic with a competitive inhibitor I2 when used in combination
Dyngo-4a
A5HZZ9
endocytic inhibitor of BoNT/A neurotoxicity through dynamin inhibition, competitive inhibition. Complete inhibition of the BoNT/A light chain at 0.02 mM
expoxomicin
-
increases ubiquitination of BoNT/B light chain in neuronal cells. Ubiquitination in vitro and in cells decreases the biological activity of BoNT/B light chain
ganglioside GT1b glycoconjugate
-
the synthetic glycoconjugates based on GT1b prevents SNAP25 cleavage in spinal cord cells of rat embryos
GGPPAPPPNLTSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ
-
residues 17-58 of vesicle-associated membrane protein VAMP
Gln-Phe-Glu-Thr
-
synthetic peptide containing cleavage site of synaptobrevin, inhibits toxin action on buccal ganglion of Aplysia californica, serotype BoNT/B, not A or E
LQQTQAQVDEVVDIMRVNVDKVLERDQ
-
residues 32-58 of vesicle-associated membrane protein VAMP. Inhibitor exhibits a high degree of specificity for BoNT F, compared to other BoNT serotypes
methyl 3alpha-(N-[(7-chloroquinolin-4-yl)amino]ethyl)amino,7alpha,12alpha-diacetoxy-5beta-cholan-24-oate
-
-
methyl 3alpha-(N-[(7-chloroquinolin-4-yl)amino]ethyl)oxy,7alpha,12alpha-diacetoxy-5beta-cholan-24-oate
-
9% inhibition at 0.05 mM
methyl 3alpha-amino-7alpha,12alpha-diacetoxycholan-24-oate
-
13% inhibition at 0.05 mM
methyl 3beta-(N-[(7-chloroquinolin-4-yl)amino]ethyl)amino,7alpha,12alpha-diacetoxy-5beta-cholan-24-oate
-
-
methylamine hydrochloride
-
affects the acidification step, acts to inhibit by neutralizing the endosomal pH and show antagonism against BoNT-induced paralysis
N'-(2-(dimethylamino)ethyl)-2-(4-(4-(N'-2-(dimethylaminoethyl)carbamimidoyl)phenoxy)phenyl)-1H-indole-6-carboximidamide
-
-
N'-[(E)-(2,4,5-trihydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
A5HZZ9
-
N,N-bis(7-aminoheptyl)-1-benzyl-4-[3-(hydroxyamino)-3-oxopropyl]-5-(3-hydroxy-3,3-diphenylpropyl)-1H-pyrrole-2-carboxamide
-
a tetrasubstituted pyrrole inhibitor
N-(2,6-dimethylphenyl)-2-(pyridine-4-carbonyl)hydrazine-1-carbothioamide
-
28% inhibition at 0.02 mM
N-(2-chlorophenyl)-2-(pyridine-4-carbonyl)hydrazine-1-carbothioamide
-
19% inhibition at 0.02 mM
N-(3alpha,7alpha,12alpha-triacetoxy-5beta-cholan-24-yl)-N'-(7'-chloroquinolin-4'-yl)-ethane-1,2-diamine
-
-
N-(4-bromobenzyl)-N'-(7-chloroquinolin-4-yl)ethane-1,2-diamine
P10845
69% inhibition at 0.02 mM
N-(4-bromobenzyl)-N'-(7-chloroquinolin-4-yl)propane-1,3-diamine
P10845
68% inhibition at 0.02 mM
N-(4-tert-butylbenzyl)-N'-(7-chloroquinolin-4-yl)ethane-1,2-diamine
P10845
47% inhibition at 0.02 mM
N-(4-tert-butylbenzyl)-N'-(7-chloroquinolin-4-yl)propane-1,3-diamine
P10845
50.28% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(4-fluorobenzyl)ethane-1,2-diamine
P10845
68% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(4-fluorobenzyl)propane-1,3-diamine
P10845
50.09% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(4-methoxybenzyl)ethane-1,2-diamine
P10845
18% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(4-methoxybenzyl)propane-1,3-diamine
P10845
14% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(pyridin-3-ylmethyl)ethane-1,2-diamine
P10845
25% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(pyridin-3-ylmethyl)propane-1,3-diamine
P10845
39.89% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(pyridin-4-ylmethyl)ethane-1,2-diamine
P10845
24% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-(pyridin-4-ylmethyl)propane-1,3-diamine
P10845
42.29% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-adamantylethane-1,2-diamine
P10845
51.4% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-[(4-methoxypyridin-3-yl)methyl]ethane-1,2-diamine
P10845
19% inhibition at 0.02 mM
N-(7-chloroquinolin-4-yl)-N'-[(4-methoxypyridin-3-yl)methyl]propane-1,3-diamine
P10845
43.25% inhibition at 0.02 mM
N-(methyl 7alpha,12alpha-diacetoxy-5beta-cholan-24-oate,3alpha-yloxy)-ethyl-N'-(7-chloroquinolin-4-yl)-ethane-1,2-diamine
-
62% inhibition at 0.05 mM
N-([1,1'-biphenyl]-4-ylmethyl)-1-(2,5-dimethoxybenzyl)-1H-1,2,4-triazole-3-carboxamide
A5HZZ9
-
N-([1,1'-biphenyl]-4-ylmethyl)-1-[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]-1H-1,2,4-triazole-3-carboxamide
A5HZZ9
-
N-([1,1'-biphenyl]-4-ylmethyl)-1H-1,2,4-triazole-3-carboxamide
A5HZZ9
-
N-Ac-CRATKML
P10845
an inhibitory peptide, structure of the serotype A toxin light chain with an inhibitory peptide bound at the catalytic Zn(II) ion, the peptide is bound with the Cys Sgamma atom coordinating the metal ion, overview
N-acetyl neuraminic acid
-
both binding and permeation of toxins are potently inhibited by N-acetyl neuraminic acid in the cell culture mediumor by treatment of the cells with neuraminidase, but neither galactose, lactose nor N-acetyl galactosamine inhibit binding or permeation of toxins
N-benzyl-N'-(7-chloroquinolin-4-yl)ethane-1,2-diamine
P10845
52% inhibition at 0.02 mM
N-benzyl-N'-(7-chloroquinolin-4-yl)propane-1,3-diamine
P10845
51.83% inhibition at 0.02 mM
N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)ethane-1,2-diamine
P10845
23% inhibition at 0.02 mM
N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)propane-1,3-diamine
P10845
35.87% inhibition at 0.02 mM
N-[3-(benzyloxy)phenyl]-2-[(2,5-dimethoxybenzyl)amino]acetamide
A5HZZ9
-
N-[3-(benzyloxy)phenyl]-2-[[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]amino]acetamide
A5HZZ9
-
N1-(2-cyclopropylethyl)-3-(2,4-dichlorophenyl)-N5-hydroxypentanediamide
A5HZZ9
-
N1-(4-bromophenyl)-3-(2,4-dichlorophenyl)-N5-hydroxypentanediamide
A5HZZ9
-
N1-(6-(6-(4,5-dihydro-1H-imidazol-2-yl)benzo[b]thiophen-2-yl)-pyridine-3-yl)ethane-1,2-diamine
-
-
N1-(7-chloroquinolin-4-yl)-ethane-1,2-diamine
-
33% inhibition at 0.05 mM
N1-(7-chloroquinolin-4-yl)-propane-1,3-diamine
-
22% inhibition at 0.05 mM
NSC 240898
-
NSC 240898, a potent BoNT/A LC endopeptidase inhibitor, 75% inhibition at 0.02 mM, no cytotoxicity
phorbol 12-myristate 13-acetate
-
increases ubiquitination of BoNT/B light chain in neuronal cells. Ubiquitination in vitro and in cells decreases the biological activity of BoNT/B light chain
PPPNLTSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ
-
residues 22-58 of vesicle-associated membrane protein VAMP. Inhibitor exhibits a high degree of specificity for BoNT F, compared to other BoNT serotypes
S132B-C11
-
a RNA aptamer that inhibits the enzyme's endopeptidase activity in a non-competitive manner. The core sequence is GACAGCGUGCCUAGAAGUCCAAGCUUAAAUAACCACGCUCGACAAGC, structure, overview
-
S132B-C12
-
a RNA aptamer that inhibits the enzyme's endopeptidase activity in a non-competitive manner. The core sequence is ACAACCCGGAACAACGUCUAACAGUGUACCAUAACCCGGCAUUCA, structure, overview
-
S132B-C22
-
a RNA aptamer that inhibits the enzyme's endopeptidase activity in a non-competitive manner. The core sequence is AUUCGGGCCCAGGAACCAACUAUAUAAAUGUCCCGAAUGCUUCGACG, structure, overview
-
single-domain llama antibody Aa1
-
most potent antibody isolated from a single domain VHH, i.e. camelid heavy-chain variable region derived from heavy-chain-only antibody, antibodies, it is resistant to heat denaturation and reducing conditions. The Aa1 paratope coincides with an alpha-helical portion of the SNAP25 substrate. Structure of BoNT/A Lc-Aa1 VHH complex and inhibition mechanism, overview
-
synaptotagmin II luminal domain
-
the luminal domain of syt II, syt II-LD, inhibits the toxicity of BoNT/B by interfering with the toxin-receptor interaction. It contains toxin-binding sites that have a high affinity for BoNT/B heavy chain. Recombinant syt II-LD in vivo provides protection against BoNT/B intoxication in mice models to about 30% survivals at 0.27 mg/ml of sytII-LD, the neutralization effect is improved by using gangliosides to 60% survivals. Syt II-LD specifically binds to BoNT/B compared to other BoNT serotypes, overview
-
THF-toosendanin
-
tetrahydrofuran analogue of toosendanin, selectively arrests the light chain translocation step of intoxication with subnanomolar potency, and increases the unoccluded heavy chain channel propensity to open with micromolar efficacy, inhibitory profile on light chain translocation, overview. The bimodal modulation by toosendanin depends on the dynamic interactions between channel and cargo, highlighting their tight interplay during the progression of LC transit across endosomes
toosendanin
-
i.e. TSDN, selectively arrests the light chain translocation step of intoxication with subnanomolar potency, and increases the unoccluded heavy chain channel propensity to open with micromolar efficacy, inhibitory profile on light chain translocation, overview. The bimodal modulation by toosendanin depends on the dynamic interactions between channel and cargo, highlighting their tight interplay during the progression of LC transit across endosomes. Toosendanin modulates both cargo-dependent and cargo-free activities of the BoNT/E protein-conducting channel
tris-(2-carboxyethyl)-phosphine hydrochloride
-
i.e. TCEP, a non-odorous, oxygen-insensitive, non-toxic sulfhydryl reducing compound, reduces proteolytic activity of BoNT/B in human neuronal SHSY-5Y cells at higher concentrations above 4 mM, protects against BoNT/B inhibition of noradrenaline release, achieving 72% of the release from un-intoxicated controls. TCEP significantly changes the conformation of BoNT/B holotoxin. But TCEP does not fragment un-nicked BoNT/B holotoxin
Triticum vulgaris lectin
-
a known competitive antagonist of BoNT, inhibits the activation of neurit outgrowth by BoNT/A
-
TSNRRLQQTQAQVDEVVDIMRVNVDKVLERDQ
-
residues 27-58 of vesicle-associated membrane protein VAMP. Inhibitor exhibits a high degree of specificity for BoNT F, compared to other BoNT serotypes
VAMP 22-58/Gln58D-cysteine
a substrate-based inhibitor, that binds to BoNT F in the canonical direction but is positioned specifically via three major exosites away from the active site
-
VAMP 27-58/Gln58D-cysteine
a substrate-based inhibitor, that binds to BoNT F in the canonical direction but is positioned specifically via three major exosites away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid
-
VVDIMRVNVDKVLERDQ
-
residues 42-58 of vesicle-associated membrane protein VAMP. Inhibitor exhibits a high degree of specificity for BoNT F, compared to other BoNT serotypes
Zn2+
-
addition of exogenous ZnCl2 to the assay mixture reduces the activity of BoNT/Am activity ratio of wild-type and mutant enzymes in presence or absence of ZnCl2, overview
[[(5-[[1-(4-ammoniobutyl)-2-phenyl-1H-indol-6-yl]carbonyl]-2-phenylthiophen-3-yl)acetyl]amino]oxidanide
-
synthesis and binding structure, overview, multiple molecular dynamics simulations of the endopeptidase in complex with inhibitor 1 using the dummy atom approach, overview
(2E)-3-(2,4-dichlorophenyl)-N-hydroxyprop-2-enamide
-
a synthetic hydroxamate, D-chicoric acid is synergistic with a competitive inhibitor I2 when used in combination
4-chlorocinnamic hydroxamate
-
binding site and complex structure, overview
Chloroquine
-
the C2II channel can be blocked by chloroquine and related compounds
concanamycin A
-
the ATPase inhibitor also functions as antagonist of the acidification process
RRGC
P10845
an inhibitory substrate analogue tetrapeptide, binding structure, overview
RRGC
-
0.02 mM, 95% inhibition, most potent inhibitor. When assayed in the presence of dithiothreitol, the inhibitory effect is drastically reduced
RRGI
P10845
an inhibitory substrate analogue tetrapeptide, binding structure, overview
RRGL
P10845
an inhibitory substrate analogue tetrapeptide, binding structure, overview
RRGM
P10845
an inhibitory substrate analogue tetrapeptide, binding structure, overview
additional information
the receptor-binding domain of botulinum neurotoxin serotype B significantly delays intoxication by botulinum neurotoxin serotype B
-
additional information
-
inhibitory potency and activity-structure relationship of 4-amino-7-chloroquinoline substructure-based compounds, molecular modeling, overview, no inhibition by methyl cholate triacetate
-
additional information
-
analysis of Echinacea components in inhibition of BoNT/A protease, overview
-
additional information
-
BoNT/B LC is processed for removal via the proteasome-dependent degradation pathway after ubiquitination in neuronal cells
-
additional information
-
capsaicin interacts with TRPV1 receptors, transient receptor potential proteins of the vanilloid subfamily, on motor nerve endings to reduce BoNT/A uptake into Neuro 2a cells via a Ca2+-dependent mechanism, but capsaicin fails to protect against the neuroparalytic effects of BoNT/A. Capsaicin protects muscle functions and electromygraphic activity from the incapacitating effects of BoNT/A. Capsazepine pretreatment antagonizes the protective effect of capsaicin on acetylcholine release at high frequencies
-
additional information
-
construction of a non-immune llama single-domain library for display on the surface of Saccharomyces cerevisiae and identification of a single-domain llama antibody that potently inhibits the enzymatic activity of BoNT/A light chain by binding to the non-catalytic alpha-exosite binding region, overview
-
additional information
P10845
construction of type A-specific monoclonal antibodies using antigene heavy chain antibody fragment VH/VHH from a nonimmune camel, primers specific to human VH gene segments, and recombinant expression in phagemid-transformed Escherichia coli. The selected antibodies inhibiting the endopeptidase activity of BoTxA light chain and of botulism in hosts in vivo. Molecular docking and interface binding of BoTxA/LC and antibody VHH17
-
additional information
-
development and synthesis of small molecule inhibitors of BoNTA endopeptidase, that antagonize the extracellular or intracellular toxin, in vivo pharmacokinetics in mice, overview. Extended multiple molecular dynamics simulations of inhibitor-enzyme complex formations, overview
-
additional information
-
development of llama single domain antibodies specific for the seven botulinum neurotoxin serotypes as heptaplex immunoreagents. A single llama is immunized with a cocktail of seven BoNT toxoids to generate a phage display library of single domain antibodies, sdAb, VHH or nanobodies, which are selected on live toxins. Several sdAb act as both captor and tracer for several toxin and toxin complexes suggesting sdAb can be used as architectural probes to indicate BoNT oligomerisation, cross reactivities, overview
-
additional information
-
development of specific potent inhibitors of BoNT/A light chain, structure-activity relationship studies, overview
-
additional information
-
evaluation of relevant and available in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors. BoNT intoxication steps as targets for inhibitors, schematic overview. Because all BoNT serotypes require the acidification step for inducing muscle failure, developing pan inhibitors that target this stage is an attractive approach. The cell entry of the toxin is inhibited by plant and animal lectines, glycoconjugates, and antibodies. The SNARE cleavage is inhibited by small molecule, peptide, and peptidomimetic inhibitors
-
additional information
-
identification of three RNA aptamers from a ssDNA random library through SELEX-process, which bind strongly to the light chain of type A BoNT and inhibit the endopeptidase activity, with IC50 in low nM range. Inhibition kinetic studies reveal low nM KI and non-competitive nature of their inhibition, enzyme docking study, and inhibition kinetics, overview
-
additional information
-
inhibition of enzymatic activity of botulinum neurotoxins/A1, /A2, and /A3 by a panel of monoclonal anti-BoNT/A antibodies
-
additional information
-
inhibitor virtual screening performed by computationally docking compounds of the NCI database into the active site of BoNT/A light chain, inhibition studies in neuroblastoma N2a cell-based and tissue-based mouse phrenic nerve hemidiaphragm assays, overview. Five quinolinol-based analogues effectively neutralize BoNT/A toxicity, with CB 7969312 exhibiting ex vivo protection at 500 nM
-
additional information
-
monoclonal antibodies F1-2 and F1-40 do not inhibit the catalytic activity of BoNT/A, but inhibit the entry of the toxin into host neuronal cells, leading to reduced toxicity to mice, and block intracellular SNAP25 cleavage, overview
-
additional information
-
regions on BoNT/B that bind to blocking antibodies, synaptotagmin, or gangliosides, recognition pattern, overview
-
additional information
-
semisynthetic strategy to identify inhibitors based on toosendanin, a traditional Chinese medicine reported to protect from BoNT intoxication, overview. No inhibition by deacetylted toosendanin and by toosendanin ketone and lactone analogues
-
additional information
-
the toxicity of the enzyme is reduced in absence of gangliosides
-
additional information
-
a tetrapeptide provides an optimum length as the most efficient peptide inhibitor that binds at the active site normally occupied by the substrate. The peptides survive within neurons for at least 40 h and inhibit BoNT/A activity within two primary neuronal cells without showing any apparent cellular toxicity
-
additional information
-
peptide HN729-845(corresponding to the BoNT/A region comprising heavy-chain N-terminal domain residues 729 to 845) is able to inhibit the binding of 125I-labeled serotype BoNT/A to synaptosomes
-
additional information
-
the C-terminal peptides of LcB-1, LcC1-1, LcD-1, and LcF-1 show no inhibitory effect
-
additional information
-
the recombinant subtype A4 neurotoxin is effectively neutralized by botulism heptavalent antitoxin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-phenyl-2-acylguanidyl thiophenes
-
compounds containing a 2-acylthiophene moiety as a zinc-binding functionality, combined with acylguanidyl groups as an arginine side chain mimetic, structure-activity relationship of 5-phenyl-2-acylguanidyl thiophene activators of BoNT LC/A under standard screening conditions, overview
5-[3-(butylsulfanyl)phenyl]-N-carbamimidoylthiophene-2-carboxamide
-
4fold activation of BoNT LC/A
5-[4-(butylsulfanyl)phenyl]-N-carbamimidoylthiophene-2-carboxamide
-
7fold activation, BoNT LC/A activation profile, overview
N-carbamimidoyl-5-[3-(ethylsulfanyl)phenyl]thiophene-2-carboxamide
-
4fold activation of BoNT LC/A
N-carbamimidoyl-5-[3-(methylsulfanyl)phenyl]thiophene-2-carboxamide
-
3fold activation of BoNT LC/A
N-carbamimidoyl-5-[4-(ethylsulfanyl)phenyl]thiophene-2-carboxamide
-
3.5fold activation of BoNT LC/A
N-carbamimidoyl-5-[4-(propylsulfanyl)phenyl]thiophene-2-carboxamide
-
7fold activation of BoNT LC/A
tris-(2-carboxyethyl)-phosphine hydrochloride
-
i.e. TCEP, a non-odorous, oxygen-insensitive, non-toxic sulfhydryl reducing compound, activates proteolytic activity of BoNT/B in human neuronal SHSY-5Y cells maximally at 1mM, protects against BoNT/B inhibition of noradrenaline release, achieving 72% of the release from un-intoxicated controls. TCEP significantly changes the conformation of BoNT/B holotoxin
Triton X-100
-
stimulates the catalytic efficiency of serotype A 35fold
bovine serum albumin
stimulates the subtype BoNT/A hydrolysis of synthetic peptide substrates
-
DTT
near-complete conversion of the enzyme SC to a disulfide-linked DC in the presence of DTT
Proteases
-
activation by rapid cleavage of MW 150000 polypeptide chain and generation of active di-chain neurotoxin
-
additional information
-
stimulation specific to serum albumins, bovine gamma globulin, ovalbumin, lysozyme, ribonuclease, and gelatin have no effect
-
additional information
-
identification of a small molecule scaffold based on 2-acyl guanidyl-5-phenyl thiophenes that strongly activates BoNT LC/A catalytic activity through an apparent reduction in KM activator screening, overview
-
additional information
-
nicking of the single chain BoNT/E to the dichain form is associated with 100fold increase in toxicity, activation mechanism of botulinum neurotoxin type E upon nicking and subsequent reduction of disulfide bond, overview
-
additional information
-
the presence of neurotoxin associated proteins enhances the oral toxicity of the neurotoxin significantly. Hemagglutinin Hn-33 makes up the largest fraction of neurotoxin associated proteins in BoNT/AC and strongly protects BoNT/A against proteases of the gastrointestinal tract
-
additional information
-
the toxins are synthesized as single polypeptide chains containing both HC and LC that are activated after undergoing posttranslational proteolysis. All BoNT serotypes require the acidification step for inducing muscle failure
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0709
Ac-ERDQKLSELDDRADALQAG-(7-methoxy-4-methylcoumaryl)Lys-SQ-diaminopropionic acid(2,4-dinitrophenyl)-ESSAAKLKRKYWWKNLK-NH2
-
pH 7.4, 22°C
0.00013
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
0.00079
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
0.011
Ac-KSDSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)LGSG-NH2
-
pH 7.4, 37°C
0.013
Ac-SNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
0.10058
SNAPtide 520
-
botulinum neurotoxin type A, at pH 7.4 and 37°C
-
0.0308
SNAPtide 521
-
recombinant light chain-translocation domain, at pH 7.4 and 37°C
-
0.0043
vesicle-associated membrane protein-1
at pH 7.1 and 37°C
-
0.8
SNAP-25
-
pH 7.4, 23°C, mutant light chain + translocation domain
-
3.6
SNAP-25
-
full-length light chain of botulinum toxin A, in 50 mM HEPES, pH 7.4, at 37°C
-
2.92
SNAP25
-
pH 7.4, 37°C, recombinant wild-type enzyme in absence of exogenous ZnCl2
-
4.81
SNAP25
-
pH 7.4, 37°C, recombinant wild-type enzyme in presence of exogenous ZnCl2
-
0.0079
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, wild-type enzyme
-
0.0097
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E335A
-
0.01
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E335Q
-
0.0112
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E249A
-
0.0112
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme R347A
-
0.0113
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E158A/T159A/N160A
-
0.0172
VAMP-2
subtype BoNT/F5, untagged, pH and temperature not specified in the publication
-
0.0231
VAMP-2
His6-tagged subtype BoNT/F7, pH and temperature not specified in the publication
-
0.00209
vesicle-associated membrane protein-2
mutant enzyme R372A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00219
vesicle-associated membrane protein-2
mutant enzyme R63A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00226
vesicle-associated membrane protein-2
mutant enzyme R63E, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.0024
vesicle-associated membrane protein-2
mutant enzyme L200D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00291
vesicle-associated membrane protein-2
wild type enzyme, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00324
vesicle-associated membrane protein-2
mutant enzyme F50D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.0033
vesicle-associated membrane protein-2
mutant enzyme Y168D/L200D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00356
vesicle-associated membrane protein-2
mutant enzyme I191D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00446
vesicle-associated membrane protein-2
mutant enzyme F50D/I191D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00481
vesicle-associated membrane protein-2
mutant enzyme F50A/I191A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.00513
vesicle-associated membrane protein-2
-
wild type enzyme, pH and temperature not specified in the publication
-
0.00796
vesicle-associated membrane protein-2
mutant enzyme I151D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.0099
vesicle-associated membrane protein-2
mutant enzyme W315A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.01186
vesicle-associated membrane protein-2
mutant enzyme P154D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.0287
vesicle-associated membrane protein-2
enzyme subtype BoNT/F1, at pH 6.8 and 37°C
-
0.03245
vesicle-associated membrane protein-2
mutant enzyme W44A/I152A/P154A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.03287
vesicle-associated membrane protein-2
mutant enzyme R23D/H132A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.03556
vesicle-associated membrane protein-2
mutant enzyme H132Q, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.0441
vesicle-associated membrane protein-2
enzyme subtype BoNT/F9, at pH 6.8 and 37°C
-
0.04763
vesicle-associated membrane protein-2
mutant enzyme W315D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.0701
vesicle-associated membrane protein-2
enzyme subtype BoNT/F6, at pH 6.8 and 37°C
-
0.2535
vesicle-associated membrane protein-2
-
pH and temperature not specified in the publication
-
additional information
additional information
-
kinetics of mutant enzymes, overview
-
additional information
additional information
-
Michaelis-Menten kinetics, overview
-
additional information
additional information
-
thermodynamics and kinetics of wild-type and mutant enzymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.81
Ac-ERDQKLSELDDRADALQAG-(7-methoxy-4-methylcoumaryl)Lys-SQ-diaminopropionic acid(2,4-dinitrophenyl)-ESSAAKLKRKYWWKNLK-NH2
-
pH 7.4, 22°C
1.15
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
2.08
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
1.01
Ac-KSDSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)LGSG-NH2
-
pH 7.4, 37°C
0.79
Ac-SNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
0.052
SNAPtide 521
-
recombinant light chain-translocation domain, at pH 7.4 and 37°C
-
0.09
SNAP-25
-
pH 7.4, 23°C, mutant light chain + translocation domain
-
38.1
SNAP-25
-
full-length light chain of botulinum toxin A, in 50 mM HEPES, pH 7.4, at 37°C
-
0.41
SNAP25
-
pH 7.4, 37°C, recombinant wild-type enzyme in absence of exogenous ZnCl2
-
0.41
SNAP25
-
pH 7.4, 37°C, recombinant wild-type enzyme in presence of exogenous ZnCl2
-
12.35
SNAP25
-
pH 7.4, 37°C, recombinant wild-type enzyme in absence of exogenous ZnCl2
-
12.39
SNAP25
-
pH 7.4, 37°C, recombinant wild-type enzyme in presence of exogenous ZnCl2
-
0.00075
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E335Q
-
0.0058
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme R347A
-
0.144
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E335A
-
0.4
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E249A
-
0.836
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E158A/T159A/N160A
-
3.13
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, wild-type enzyme
-
4.29
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, wild-type enzyme
-
6.08
synaptosome-associated protein SNAP-25
-
37°C, pH 7.4, mutant enzyme E158A/T159A/N160A
-
64.69
VAMP-2
His6-tagged subtype BoNT/F7, pH and temperature not specified in the publication
-
594.6
VAMP-2
subtype BoNT/F5, untagged, pH and temperature not specified in the publication
-
0.02
vesicle-associated membrane protein-2
mutant enzyme I151D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.04
vesicle-associated membrane protein-2
mutant enzyme F50D/I191D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.12
vesicle-associated membrane protein-2
mutant enzyme Y168D/L200D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.15
vesicle-associated membrane protein-2
mutant enzyme R63E, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.17
vesicle-associated membrane protein-2
mutant enzyme R372A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.28
vesicle-associated membrane protein-2
mutant enzyme F50A/I191A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.4
vesicle-associated membrane protein-2
mutant enzyme R63A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.81
vesicle-associated membrane protein-2
mutant enzyme L200D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
0.86
vesicle-associated membrane protein-2
mutant enzyme H132Q, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
1.4
vesicle-associated membrane protein-2
mutant enzyme I191D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
1.52
vesicle-associated membrane protein-2
mutant enzyme W315A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
1.6
vesicle-associated membrane protein-2
mutant enzyme F50D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
2.38
vesicle-associated membrane protein-2
mutant enzyme R23D/H132A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
3.92
vesicle-associated membrane protein-2
mutant enzyme W315D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
5.86
vesicle-associated membrane protein-2
mutant enzyme W44A/I152A/P154A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
6.35
vesicle-associated membrane protein-2
mutant enzyme P154D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
6.88
vesicle-associated membrane protein-2
wild type enzyme, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
7.37
vesicle-associated membrane protein-2
enzyme subtype BoNT/F6, at pH 6.8 and 37°C
-
12.43
vesicle-associated membrane protein-2
enzyme subtype BoNT/F9, at pH 6.8 and 37°C
-
17.3
vesicle-associated membrane protein-2
-
pH and temperature not specified in the publication
-
23.25
vesicle-associated membrane protein-2
enzyme subtype BoNT/F1, at pH 6.8 and 37°C
-
938.9
vesicle-associated membrane protein-2
-
wild type enzyme, pH and temperature not specified in the publication
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8850
Ac-IIGNLRH(Nle)ALD(Nle)GNEIDTQNRQIDRI(Nle)EKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
2630
Ac-IIGNLRHMALDMGNEIDTQNRQIDRIMEKADSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
92
Ac-KSDSNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)LGSG-NH2
-
pH 7.4, 37°C
61
Ac-SNKTRIDEAN(pNO2-Phe)RA(1-pyrenylalanine)K(Nle)L-NH2
-
pH 7.4, 37°C
1.6
SNAPtide 521
-
recombinant light chain-translocation domain, at pH 7.4 and 37°C
-
0.11
SNAP-25
-
pH 7.4, 23°C, mutant light chain + translocation domain
-
2800
VAMP-2
His6-tagged subtype BoNT/F7, pH and temperature not specified in the publication
-
34570
VAMP-2
subtype BoNT/F5, untagged, pH and temperature not specified in the publication
-
2.5
vesicle-associated membrane protein-2
mutant enzyme I151D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
8.9
vesicle-associated membrane protein-2
mutant enzyme F50D/I191D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
24
vesicle-associated membrane protein-2
mutant enzyme H132Q, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
36
vesicle-associated membrane protein-2
mutant enzyme Y168D/L200D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
58
vesicle-associated membrane protein-2
mutant enzyme F50A/I191A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
66
vesicle-associated membrane protein-2
mutant enzyme R63E, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
68.3
vesicle-associated membrane protein-2
-
pH and temperature not specified in the publication
-
72
vesicle-associated membrane protein-2
mutant enzyme R23D/H132A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
81
vesicle-associated membrane protein-2
mutant enzyme R372A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
82
vesicle-associated membrane protein-2
mutant enzyme W315D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
150
vesicle-associated membrane protein-2
mutant enzyme W315A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
180
vesicle-associated membrane protein-2
mutant enzyme R63A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
180
vesicle-associated membrane protein-2
mutant enzyme W44A/I152A/P154A, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
281.7
vesicle-associated membrane protein-2
enzyme subtype BoNT/F9, at pH 6.8 and 37°C
-
340
vesicle-associated membrane protein-2
mutant enzyme L200D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
390
vesicle-associated membrane protein-2
mutant enzyme I191D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
490
vesicle-associated membrane protein-2
mutant enzyme F50D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
540
vesicle-associated membrane protein-2
mutant enzyme P154D, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
810
vesicle-associated membrane protein-2
enzyme subtype BoNT/F1, at pH 6.8 and 37°C
-
1050
vesicle-associated membrane protein-2
enzyme subtype BoNT/F6, at pH 6.8 and 37°C
-
2360
vesicle-associated membrane protein-2
wild type enzyme, in 10 mM Tris-HCl (pH 7.6) and 20 mM NaCl, at 37°C
-
183020
vesicle-associated membrane protein-2
-
wild type enzyme, pH and temperature not specified in the publication
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00016
(3R)-3-(2,4-dichlorophenyl)-N,5-dihydroxypentanamide
-
pH 7.4, 22.5°C
0.0017
(3R)-3-(4-chlorophenyl)-N,5-dihydroxypentanamide
-
pH 7.4, 22.5°C
0.0038
([[5-[[1-(4-ammoniobutyl)-2-phenyl-1H-indol-6-yl]carbonyl]-2-(3-hydroxyphenyl)thiophen-3-yl]acetyl]amino)oxidanide
-
pH 7.3, 37°C, hydroxyl-containing analogue of BoNTA endopeptidase
0.007
2-(5-{[1-(4-aminobutyl)-2-phenyl-1H-indol-6-yl]carbonyl}-2-phenylthiophen-3-yl)-N-hydroxyacetamide
-
pH not specified in the publication, temperature not specified in the publication
0.00129
2-(9H-fluorene-2-carbonyl)benzoic acid
-
pH and temperature not specified in the publication
0.004
2-[5-{[1-(4-aminobutyl)-2-phenyl-1H-indol-6-yl]carbonyl}-2-(3-hydroxyphenyl)thiophen-3-yl]-N-hydroxyacetamide
-
pH not specified in the publication, temperature not specified in the publication
0.0021
3-(2,4-dichlorophenyl)-5-(4-fluorophenethoxy)-N-hydroxypentanamide
A5HZZ9
at pH 7.4 and 37°C
0.001
3-(2,4-dichlorophenyl)-N1-(4-fluoro-2-methoxyphenyl)-N5-hydroxypentanediamide
A5HZZ9
at pH 7.4 and 37°C
0.00046
3-hydroxy-N'-[(E)-(3,4,5-trihydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
A5HZZ9
pH and temperature not specified in the publication
0.00453
32-mer C-terminal peptide of LcA
-
full-length light chain of botulinum toxin A, in 50 mM HEPES, pH 7.4, at 37°C
-
0.0062
4-chloro-(3-fluorophenyl)methyl benzenesulfonamide
-
at pH 7.4 and 25°C
0.0032
4-chloro-N-[(4-fluorophenyl)methyl] pyridin-3-amine
-
at pH 7.4 and 25°C
0.00058
4-[((2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2R)-2-phenylethylcarbamoyl)-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl)]benzoic acid
-
-
0.00081
4-[((2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-(4-hydroxyphenyl)ethylcarbamoyl)-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl)]benzoic acid
-
-
0.00035
4-[((2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1H-indol-3-yl)ethylcarbamoyl]-3(S)sulfanylpropyl)]benzoic acid
-
-
0.0005
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-(3H-imidazol-4-yl)ethylcarbamoyl]-(2S)-2-biphenyl-4-ylethylcarbamoyl)-3(S)sulfanylpropyl]benzoic acid
-
-
0.00054
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-methylbutylcarbamoyl-(2S)-2-biphenyl-4-ylethylcarbamoyl]-3(S)-sulfanylpropyl)] benzoic acid
-
-
0.00054
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2R)-2-biphenyl-4-yl-ethylcarbamoyl]-3(S)sulfanylpropyl]benzoic acid
-
-
0.00017
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1-methyl-1H-indol-3-yl)ethylcarbamoyl]-3(S)sulfanylpropyl] benzoic acid
-
-
0.00022
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-naphthalen-1-yl-ethylcarbamoyl]-3(S)sulfanylpropyl] benzoic acid
-
-
0.00016
4-[(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl]-3(S)sulfanylpropyl)] benzoic acid
-
-
0.00002
4-[(2S)-2-amino-3-[1-(2S)-2-benzol[beta]thiophen-3-yl-1-benzylcarbamoylethylcarbamoyl-(2S)-2-biphenyl-4-yl-ethylcarbamoyl]-3-(S)-sulfanylpropyl] benzoic acid
-
-
0.0018
chicoric acid iso-propyl ester
A5HZZ9
pH and temperature not specified in the publication
0.00032
Dyngo-4a
A5HZZ9
pH and temperature not specified in the publication
0.00046
N-hydroxy-2-(tricyclo[3.3.1.13,7]dec-1-yl)acetamide
A5HZZ9
at pH 7.4 and 37°C
0.007
[[(5-[[1-(4-ammoniobutyl)-2-phenyl-1H-indol-6-yl]carbonyl]-2-phenylthiophen-3-yl)acetyl]amino]oxidanide
-
pH 7.3, 37°C, wild-type BoNTA endopeptidase
additional information
additional information
P10845
binding and inhibition kinetics of antigene heavy chain antibody fragment VH/VHH-specific antibodies, overview
-
additional information
additional information
-
inhibition kinetics and mechanism of Echinacea components on BoNT/A, overview
-
additional information
additional information
-
the non-fluorescent substrate GST-SNAP-25(141-206) is a competitive inhibitor in the fluorometric assay for CsY and YsCsY with Ki values of 0.0076 and 0.0045 mM, respectively
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
(2E)-2-(1H-benzimidazol-2-yl)-3-(3-iodo-4-methoxyphenyl)prop-2-enenitrile
Clostridium botulinum
-
37°C, pH not specified in the publication
0.012
(2E)-3-[4-chloro-2-(iminomethyl)phenyl]-N-hydroxyprop-2-enamide
Clostridium botulinum
-
-
0.0051
(2E)-3-[4-chloro-2-(methylsulfanyl)phenyl]-N-hydroxyprop-2-enamide
Clostridium botulinum
-
-
0.017
(2E)-3-[4-chloro-2-(methylsulfonyl)phenyl]-N-hydroxyprop-2-enamide
Clostridium botulinum
-
-
0.0006
(2E)-3-[4-chloro-2-(trifluoromethyl)phenyl]-N-hydroxyprop-2-enamide
Clostridium botulinum
-
-
0.01
(3alpha,5beta,7alpha,12alpha,17alpha)-24-([2-[(7-chloroquinolin-4-yl)amino]ethyl]amino)cholane-3,7,12-triyl triacetate
Clostridium botulinum
P10845
pH and temperature not specified in the publication
0.001
(3R)-3-(2,4-dichlorophenyl)-N,5-dihydroxypentanamide
Clostridium botulinum
-
pH 7.4, 22.5°C
0.008
(3R)-3-(4-chlorophenyl)-N,5-dihydroxypentanamide
Clostridium botulinum
-
pH 7.4, 22.5°C
0.021
(3S)-3-(2,4-dichlorophenyl)-N,5-dihydroxypentanamide
Clostridium botulinum
-
pH 7.4, 22.5°C
0.036
(3S)-3-(4-chlorophenyl)-N,5-dihydroxypentanamide
Clostridium botulinum
-
pH 7.4, 22.5°C
0.0027
2'-((9H-fluoren-2-ylamino)carbonyl)-4,4'-bis(hydroxy(oxido)amino)[1,1'-biphenyl]-2-carboxylic acid
Clostridium botulinum
-
at pH 7.4 and 37°C
0.059
2-(1H-benzo[d]imidazol-2-yl)-3-(5-(furan-2-yl)thiophen-2-yl)acrylonitrile
Clostridium botulinum
-
37°C, pH not specified in the publication
0.086
2-(1H-benzo[d]imidazol-2-yl)-3-(biphenyl-4-yl)acrylonitrile
Clostridium botulinum
-
37°C, pH not specified in the publication
0.025
2-(4-(2,4-dichlorophenoxy)phenyl)-6-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-(2-chloro-4-cyanophenoxy)phenyl)-1H-indole-6-carbonitrile
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.03
2-(4-(2-chloro-4-cyanophenoxy)phenyl)-6-(4,5-dihydro-1H-imidazol-2-yl)indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.054
2-(4-(4-(6-(1,4,5,6-tetrahydropyrimidin-2-yl)benzo[b]thiophen-2-yl)phenoxy)phenyl)-1,4,5,6-tetrahydropyrimidine
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.0071
2-(4-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzo[b]thiophen-2-yl)phenoxy)phenyl)-4,5-dihydro-1H-imidazole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.0073
2-(4-(4-(6-(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)-1H-indol-2-yl)phenoxy)phenyl)-1,4,5,6-tetrahydropyrimidin-5-ol
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-(4-carbamoylphenoxy)phenyl)-1H-indole-6-carboxamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.025
2-(4-(4-cyanophenoxy)phenyl)-1H-indole-6-carboximidamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-(4-cyanophenoxy)phenyl)indole-6-carbonitrile
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-(6-(1,4,5,6-tetrahydropyrimidin-2-yl)benzo[b]thiophen-2-yl)phenyl)-1,4,5,6-tetrahydropyrimidine
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.043
2-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzo[b]thiophen-2-yl)-phenyl)-4,5-dihydro-1H-imidazole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-fluorophenyl)-1H-indole-6-carbonitrile
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-fluorophenyl)-1H-indole-6-carboxamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-fluorophenyl)-1H-indole-6-carboximidamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-methoxyphenyl)-1H-indole-6-carboxamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(4-methoxyphenyl)-1H-indole-6-carboximidamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.045
2-(4-methoxyphenyl)-6-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(5-(4-cyanophenoxy)pyridin-2-yl)-1H-indole-6-carbonitrile
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
2-(5-fluoro-2-pyridyl)-6-benzo[b]thiophenecarboxamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.097
2-(pyridin-2-ylamino)cyclohexa-2,5-diene-1,4-dione
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.417
2-amino-N-[3-(benzyloxy)phenyl]acetamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0007
2-methyl-7-[phenyl[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0014
2-methyl-7-[phenyl[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0046
2-methyl-7-[phenyl[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.094
2-[1-cyano-2-(3-bromo-5-methoxy-4-hydroxyphenyl)vinyl]benzimidazole
Clostridium botulinum
-
37°C, pH not specified in the publication
0.059
2-[1-cyano-2-(3-chloro-5-methoxy-4-hydroxyphenyl)vinyl]benzimidazole
Clostridium botulinum
-
37°C, pH not specified in the publication
0.04
3'-O-ethyl-dynasore
Clostridium botulinum
A5HZZ9
IC50 above 0.04 mM, pH and temperature not specified in the publication
0.0098
3,9-dichloro-6-(5,7-dichloro-9H-fluoren-2-yl)-5H-dibenzo[c,e]azepine-5,7(6H)-dione
Clostridium botulinum
-
at pH 7.4 and 37°C
0.026
3-(2,20-bithiophen-5-yl)-2-(1H-benzo-imidazol-2-yl)acrylonitrile
Clostridium botulinum
-
37°C, pH not specified in the publication
0.00097
3-(2,4-dichlorophenyl)-5-(4-fluorophenethoxy)-N-hydroxypentanamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0011
3-(2,4-dichlorophenyl)-N1-(4-fluoro-2-methoxyphenyl)-N5-hydroxypentanediamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0026
3-(2,4-dichlorophenyl)-N1-(4-fluorophenethyl)-N5-hydroxypentanediamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0067
3-(2,4-dichlorophenyl)-N1-hydroxy-N5-(4-methoxyphenethyl)pentanediamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.002
3-(2,4-dichlorophenyl)-N1-hydroxy-N5-(o-tolyl)pentanediamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.073
3-(4-(1H-imidazol-1-yl)phenyl)-2-(1H-benzoimidazol-2-yl)acrylonitrile
Clostridium botulinum
-
37°C, pH not specified in the publication
0.003
3-(4-chloro-2-methylphenyl)-N-hydroxypropanamide
Clostridium botulinum
-
pH 7.4, 22.5°C
0.04
3-hydroxy-N'-[(E)-(2-hydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
Clostridium botulinum
A5HZZ9
IC50 above 0.04 mM, pH and temperature not specified in the publication
0.00194
3-hydroxy-N'-[(E)-(3,4,5-trihydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
Clostridium botulinum
A5HZZ9
pH and temperature not specified in the publication
0.04
3-hydroxy-N'-[(E)-(3-hydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
Clostridium botulinum
A5HZZ9
IC50 above 0.04 mM, pH and temperature not specified in the publication
0.04
3H-dynasore
Clostridium botulinum
A5HZZ9
IC50 above 0.04 mM, pH and temperature not specified in the publication
0.04
3H-dyngo-4a
Clostridium botulinum
A5HZZ9
IC50 above 0.04 mM, pH and temperature not specified in the publication
0.0032
4,4'-dichloro-2'-((9H -fluoren-2-ylamino)carbonyl)[1,1'-biphenyl]-2-carboxylic acid
Clostridium botulinum
-
at pH 7.4 and 37°C
0.003
4,4'-dichloro-2'-[(5,7-dichloro-9H-fluoren-2-yl)carbamoyl][1,1'-biphenyl]-2-carboxylic acid
Clostridium botulinum
-
at pH 7.4 and 37°C
0.0058
4-chloro-(3-fluorophenyl)methyl benzenesulfonamide
Clostridium botulinum
-
at pH 7.4 and 25°C
0.0033
4-chloro-N-[(4-fluorophenyl)methyl] pyridin-3-amine
Clostridium botulinum
-
at pH 7.4 and 25°C
0.013
5-((3-bromoadamantan-1-yl)methoxy)-3-(2,4-dichlorophenyl)-N-hydroxypentanamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0054
5-(allyloxy)-3-(2,4-dichlorophenyl)-N-hydroxypentanamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0029
5-(benzyloxy)-3-(2,4-dichlorophenyl)-N-hydroxypentanamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0007
5-chloro-7-[(2,4-difluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0006
5-chloro-7-[(2,4-difluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0022
5-chloro-7-[(2,4-difluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0014
5-chloro-7-[(2-fluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0007
5-chloro-7-[(2-fluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.004
5-chloro-7-[(2-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0006
5-chloro-7-[(4-fluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0023
5-chloro-7-[(4-fluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0007
5-chloro-7-[(4-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0015
5-chloro-7-[phenyl[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0035
5-chloro-7-[phenyl[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0045
5-chloro-7-[phenyl[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.028
6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-(4-(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)phenyl)-1H-benzo[d]imidazole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.021
6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-(4-(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy)phenyl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.067
6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-{5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]pyridin-2-yl}-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
6-(3,4,5,6-tetrahydropyrimidin-2-yl)-2-(4-(3,4,5,6-tetrahydropyrimidin-2-yl)phenyl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.02
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.0245
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)phenyl)-1H-benzo[d]imidazole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.0125
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)phenyl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
6-(4,5-dihydro-1H-imidazol-2-yl)-2-(4-fluorophenyl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.069
6-(4,5-dihydroimidazol-2-yl)-2-(5-(4-(4,5-dihydroimidazol-2-yl)phenoxy)pyridine-2-yl)indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.1
6-chloro-2-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy)-phenyl)-1H-indole
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.2
6-[(2,5-dimethoxyphenyl)amino]-N-(4-phenoxybenzyl)picolinamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0023
6-[(3,6-dioxocyclohexa-1,4-dien-1-yl)amino]-N-(4-phenoxybenzyl)picolinamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0027
7-[(2,4-difluorophenyl)[(pyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0036
7-[(2,4-difluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0123
7-[(2,4-difluorophenyl)[(pyridin-3-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0044
7-[(2,4-difluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0043
7-[(2,4-difluorophenyl)[(pyrimidin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0127
7-[(2,4-difluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0014
7-[(2-fluorophenyl)[(pyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0012
7-[(2-fluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0007
7-[(2-fluorophenyl)[(pyridin-3-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0024
7-[(2-fluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.012
7-[(2-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0019
7-[(2-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0016
7-[(4-fluorophenyl)[(pyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0041
7-[(4-fluorophenyl)[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0008
7-[(4-fluorophenyl)[(pyridin-3-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0046
7-[(4-fluorophenyl)[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0042
7-[(4-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0017
7-[(4-fluorophenyl)[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0015
7-[phenyl[(pyridin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0062
7-[phenyl[(pyridin-3-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0027
7-[phenyl[(pyrimidin-2-yl)amino]methyl]quinolin-8-ol
Clostridium botulinum
-
pH and temperature not specified in the publication
0.0293
dynasore
Clostridium botulinum
A5HZZ9
pH and temperature not specified in the publication
0.007
methyl 3alpha-(N-[(7-chloroquinolin-4-yl)amino]ethyl)amino,7alpha,12alpha-diacetoxy-5beta-cholan-24-oate
Clostridium botulinum
-
-
0.017
methyl 3beta-(N-[(7-chloroquinolin-4-yl)amino]ethyl)amino,7alpha,12alpha-diacetoxy-5beta-cholan-24-oate
Clostridium botulinum
-
-
0.014
methyl 6-[(3,6-dioxocyclohexa-1,4-dien-1-yl)amino]picolinate
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0025
N'-(2-(dimethylamino)ethyl)-2-(4-(4-(N'-2-(dimethylaminoethyl)carbamimidoyl)phenoxy)phenyl)-1H-indole-6-carboximidamide
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.04
N'-[(E)-(2,4,5-trihydroxyphenyl)methylidene]benzohydrazide
Clostridium botulinum
A5HZZ9
IC50 above 0.04 mM, pH and temperature not specified in the publication
0.00625
N'-[(E)-(2,4,5-trihydroxyphenyl)methylidene]naphthalene-2-carbohydrazide
Clostridium botulinum
A5HZZ9
pH and temperature not specified in the publication
0.01
N-(3alpha,7alpha,12alpha-triacetoxy-5beta-cholan-24-yl)-N'-(7'-chloroquinolin-4'-yl)-ethane-1,2-diamine
Clostridium botulinum
-
-
0.0189
N-(7-chloroquinolin-4-yl)-N'-adamantylethane-1,2-diamine
Clostridium botulinum
P10845
pH and temperature not specified in the publication
0.04
N-([1,1'-biphenyl]-4-ylmethyl)-1-(2,5-dimethoxybenzyl)-1H-1,2,4-triazole-3-carboxamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0025
N-([1,1'-biphenyl]-4-ylmethyl)-1-[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]-1H-1,2,4-triazole-3-carboxamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.21
N-([1,1'-biphenyl]-4-ylmethyl)-1H-1,2,4-triazole-3-carboxamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.16
N-([1,1'-biphenyl]-4-ylmethyl)-2-aminoacetamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.041
N-hydroxy-4-pentylbenzamide
Clostridium botulinum
-
pH not specified in the publication, temperature not specified in the publication
0.025
N-[3-(benzyloxy)phenyl]-2-[(2,5-dimethoxybenzyl)amino]acetamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.018
N-[3-(benzyloxy)phenyl]-2-[[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]amino]acetamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0092
N1-(2-cyclopropylethyl)-3-(2,4-dichlorophenyl)-N5-hydroxypentanediamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.0064
N1-(4-bromophenyl)-3-(2,4-dichlorophenyl)-N5-hydroxypentanediamide
Clostridium botulinum
A5HZZ9
at pH 7.4 and 37°C
0.056
N1-(6-(6-(4,5-dihydro-1H-imidazol-2-yl)benzo[b]thiophen-2-yl)-pyridine-3-yl)ethane-1,2-diamine
Clostridium botulinum
-
pH 7.4, 37°C, BoNT/A light chain
0.00000047
single-domain llama antibody Aa1
Clostridium botulinum
-
pH not specified in the publication, temperature not specified in the publication
-
0.000001
VAMP 22-58/Gln58D-cysteine
Clostridium botulinum
pH not specified in the publication, temperature not specified in the publication
-
0.0000019
VAMP 27-58/Gln58D-cysteine
Clostridium botulinum
pH not specified in the publication, temperature not specified in the publication
-
0.0004
(2E)-3-(2,4-dichlorophenyl)-N-hydroxyprop-2-enamide
Clostridium botulinum
-
pH 7.4, 22.5°C
0.0009
(2E)-3-(2,4-dichlorophenyl)-N-hydroxyprop-2-enamide
Clostridium botulinum
-
pH not specified in the publication, temperature not specified in the publication
0.0008
(2E)-3-(4-chloro-2-methylphenyl)-N-hydroxyprop-2-enamide
Clostridium botulinum
-
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15.8
-
69nM purified native BoNT/A1 toxin, substrate SNAP25, pH 7.3, 37°C
additional information
additional information
-
development of a rapid quantitative assay method to distiguish the enzyme serotypes A, B, E, F, and G, evaluation, overview
additional information
-
status epilepticus induced in Mus musculus C57BL/6N. Mouse treatment with BoNT/E delays the onset of chronic epilepsy but does not inhibit the occurrence of spontaneous seizures. BoNT/E reduces loss of CA1 pyramidal neurons and dispersion of dentate granule cells. BoNT/E supresses the downregulation of reelin mRNA expression along the hippocampal fissure.
additional information
-
studies on the use of BoNT-A in rat prostates, dog prostates, human prostates for analysing effect on lower urinary tract symptoms due to benign prostatic enlargment. Human prostates: analysis of disease specific and clinical relevant values
additional information
-
163-167 U/ml by MBA assay, 153 U/ml by RSC assay
additional information
activities of wild-type and mutant BoNT/Fs
additional information
-
BoNT/A activity in muscle, twitch tension, overview
additional information
-
synaptosome capture assay for the different serotype BoNTs, synaptosome from rat brains, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
additional information
-
different serotypes were found to possess different optimal cleavage pHs
7.4
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
22
37
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37 - 50
the light chain of subtype BoNT/B loses its activity beyond 37°C, with total loss at 50°C
25 - 37
-
the enzyme shows 33% activity at 25°C compared to it optimum at 37°C
25 - 50
-
20% of maximal activity at 20°C, as the temperature is increased to 45°C, the endopeptidase activity dramatically decreases to 21% cleavage of SNAP-25, but at 50°C its enzymatic activity increases again to 64% cleavage of SNAP-25, 4% of maximal activity at 60°C
37 - 50
the light chain of subtype BoNT/E loses its activity beyond 37°C but remains active even up to 50°C, retaining about 44% activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6
-
recombinant catalytically inactive BoNT/A1 mutant H223A/E224A/H227A holoprotein, sequence calculation
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
BoNT/B; BoNT/A1, BoNT/A3, BoNT/B1, and BoNT/B4 from strains ATCC 3502, NCTC 2012, Okra, and Eklund 17B strains, respectively
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
-
BoNTs enter sensitive host cells via receptor-mediated endocytosis. Exposure of the BoNT-receptor complex to the acidic milieu of endosomes induces a conformational change, leading to the insertion of the HC into the endosomal membrane, thereby forming a transmembrane protein-conducting channel that translocates the light chain to the cytosol where it acts. Disulfide reduction prior to translocation dissociates the light chain from the heavy chain, thereby generating a channel devoid of translocation activity, the channel-forming entity is confined to HN, overview
additional information
-
expression analysis of BoNT/A2 and of BoNT/A2 toxin complexes in Clostridium botulinum strains comprising subtypes A1, A2, A3, A4, and B, immunohistochemic analysis, overview
additional information
serotype BoNT/C requires a single ganglioside as a binding receptor on neuronal cells, while serotypes BoNT/A and BoNT/B require two receptors for specific binding. Binding mechanism of the BoNT/OFD05 binding domain and its ganglioside receptors on neuronal host cells, overview
additional information
-
serotype BoNT/C requires a single ganglioside as a binding receptor on neuronal cells, while serotypes BoNT/A and BoNT/B require two receptors for specific binding. Binding mechanism of the BoNT/OFD05 binding domain and its ganglioside receptors on neuronal host cells, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the C2II binding component forms cation-selective and chloroquine-sensitive heptameric channels into lipid bilayer membranes, which is essential for C2I catalytic component transport into target cells
additional information
-
the enzyme consists of two components, which are both secreted into the target cells or the cell culturemedium, respectively
-
additional information
-
parasite enzyme component C2IIa forms ring-shaped heptamers, which bind to cell receptors and mediate the transport of component C2I into the cytosol of target cells. Receptor-bound C2IIa serves as a docking platform for C2I on the cell surface, following assembly of C2I, the toxin complex is taken up via receptor-mediated endocytosis, and finally, C2IIa facilitates translocation of C2I from acidic endosomes into the cytosol, overview
-
additional information
-
the C-terminal B domain, i.e. heavy chain, HC, is composed of two functional domains that are involved in receptor recognition and translocation of the light chain across the host cell endosomal membrane
-
additional information
-
the toxin binds to host plasma membrane of epithelial or neuronal cells, overview. Molecular modelling of Hc-N/A membrane binding via sphingomyelin-enriched membrane microdomains and phosphatidylinositol phosphates, overview
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
the light chain domain of BoNT/A specifically cleaves synaptosome associated protein of 25 kDa, resulting in the inhibition of neurotransmission at the synapse of peripheral neurons
physiological function
additional information
malfunction
-
BoNT acts on the host neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis
malfunction
-
BoNT proteases are blockers of synaptic transmission in host peripheral cholinergic nervous system synapses, they disable host synaptic vesicle exocytosis by cleaving their cytosolic SNARE, i.e. soluble NSF attachment protein receptor, substrates through cleavage by its N-terminal Zn2+-metalloprotease activity, and are the causative agent of botulism and the most poisonous protein known. Presence of BoNT heavy chain in endosomes or the light chain in the cytosol during intoxication may disrupt the host regulatory networks involved in neuronal protein homeostasis and may trigger a stress response comparable to the endoplasmic reticulum unfolded protein response
malfunction
-
BoNT/A injection induces local masseter muscle atrophy in Wistar rats, with alterations of craniofacial bone growth and development, overview
malfunction
-
the endopeptidase activity of light chain domain of BoNT causes inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism in the host
physiological function
-
after entering its target, the neuronal cell, BoNT/B is responsible for synaptobrevin-2, i.e. VAMP2, cleavage. This results in reduced neurotransmitter acetylcholine release from synaptic vesicles, yielding muscular paralysis
physiological function
-
analgesic effect of BoNT/A on neuropathic pain, e.g. chronic refractory neck pain, application on human neck and shoulder muslces
physiological function
-
BoNT/A is a metalloprotease that enters peripheral motor nerve terminals and blocks the release of acetylcholine via the specific cleavage of the synaptosomal-associated protein of 25 kDa. The C-terminus of the heavy chain. HC binds with extraordinary specificity to nerve terminals. Following receptor-mediated endocytosis and acidification of the endosome, the N-terminal portion of the heavy chain, HN, translocates LC across the vesicular membrane into the cytosol. LC acts as Zn2+-dependent endopeptidase to cleave essential protein components of the neurotransmitter release machinery, the SNARE, i.e. soluble N-ethylmaleimide-sensitive factor attachment protein receptor, proteins. This results in disruption of Ca2+-triggered fusion of synaptic vesicles with the plasma membrane. Central effects of BoNT/A and mechanism, detailed overview
physiological function
P10845
BoNT/A is an extremely potent bacterial protein toxin. The Hc fragment of BoNT/A is non-toxic, antigenic, and capable of eliciting a protective immunity in animals challenged with homologous BoNT
physiological function
-
BoNTs are extremely potent neuromuscular poisons that act through soluble N-ethylmaleimide-sensitive factor attachment protein receptor, SNARE, protein cleavage to inhibit neurotransmitter release. Ability of BoNT/A to eliminate localized transmitter and to induce nerve outgrowth.. BoNT/A potently stimulates neuritogenesis at concentrations as low as 0.01 nM in primary cultures enriched with motor neurons isolated from embryonic mouse spinal cord. Presence or absence of SNAP-25 cleavage by BoNT/A is not a determinant factor in BoNT/A-induced neuritogenesis
physiological function
-
BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action
physiological function
-
botulinum neurotoxins cleave components of the SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor, protein complex, inhibiting acetylcholine release into neuromuscular junctions, resulting in flaccid paralysis and eventual death
physiological function
-
botulinum neurotoxins elicit flaccid paralysis by cleaving SNARE proteins within peripheral neurons. BoNT/A and BoNT/B utilize synaptic vesicle protein 2, SV2, and synaptotagmin, respectively, as receptors for entry into neurons
physiological function
botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation
physiological function
-
Clostridium botulinum neurotoxin is the causative agent of botulism, a neuroparalytic disease
physiological function
-
Clostridium botulinum neurotoxins are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors, SNARE, proteins
physiological function
-
protective potential of the synaptic blocker BoNT/E, that prevents vesicle fusion via the cleavage of the SNARE, i.e. soluble NSF-attachment receptor, protein SNAP-25, i.e. synaptosomal-associated protein of 25 kDa. Acute neuroprotection by the synaptic blocker botulinum neurotoxin E in a Sprague-Dawley adult female rat model of focal cerebral ischemia. BoNT/E inhibits ET-1-induced glutamate release in the hippocampus
physiological function
-
the pharmacologic effect of Botulinumtoxin A includes a reversible blockade of acetylcholine, inhibition of other neurotransmitters, e.g. Substance P and ATP, and the downregulation of axonalexpression of purinergic P2X3- and capsaicin TPRV1-receptors at the nerve endings of the suburothelium, all leading to afferent desensibilization
physiological function
-
Botulinum neurotoxins are produced as progenitor toxin complexes by Clostridium botulinum. The progenitor toxin complexes are composed of enzyme and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver the enzyme through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich progenitor toxin complex on the intestinal lumen preceding its transport across the epithelial barriers
physiological function
P10845
non-toxic non-hemagglutinin protein forms the minimally functional progenitor toxin complex with botulinum neurotoxin which protects the enzyme in the gastrointestinal tract at acidic pH values and releases it upon entry into the circulation
physiological function
-
The botulinum neurotoxin A8 subtype causes severe botulism. The binding characteristics of the botulinum neurotoxin A8 subtype to its main neuronal protein receptor SV2C are unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to subtype BoNT/A1
physiological function
the enzyme inhibit secretion of CGRP neuropeptide neurons
additional information
-
A large toxin complex, L-TC, produced by Clostridium botulinum is composed of neurotoxin BoNT, non-toxic non-hemagglutinin, and hemagglutinin subcomponents, HA-70, -33 and -17
additional information
-
botulinum neurotoxin serotype A causes a life-threatening neuroparalytic disease known as botulism that can afflict large, unprotected populations if the toxin is employed in an act of bioterrorism
additional information
-
polysialylated ganglioside GT1b can act as a potential receptor for BoNT/A, and synthetic glycoconjugates based on GT1b prevent SNAP25 cleavage in spinal cord cells of rat embryos
additional information
-
retrograde transport and transcytosis of catalytically active BoNT/A in cells, mechanisms, overview
additional information
-
The BoNT-receptor complex enters neurons by receptor-mediated endocytosis. Synaptic vesicle protein 2, synaptotagmin I, synaptophysin, vesicle-associated membrane protein 2, and the vacuolar ATPase-proton pump are components of the BoNT-synaptic vesicle protein complex
additional information
-
the catalytic light chain, LC, of botulinum neurotoxin B is unable to enter target neuronal cells by itself. It is brought into the cell, human neuronal SHSY-5Y cells, in association with the BoNT/B heavy chain, HC, through endocytosis
additional information
-
the presence of neurotoxin associated proteins enhances the oral toxicity of the neurotoxin significantly. The whole neurotoxin complex reacts 60 times better with the complex and 35 times better with Hn-33 and NAPs compared to the purified neurotoxin suggesting stronger immunogenicity of neurotoxin associated proteins over that of purified neurotoxin and a higher potential of BoNT/AC and its associated proteins to induce host immune response. BoNT/A in its purified and complex forms induces equal immunogenic response and a 2.5fold higher immunogenic response compared to BoNT/A light and heavy chains
additional information
-
the short synthetic peptide TD-1 can facilitate effective transdermal delivery of BoNT-A through intact skin. Coadministration of TD-1 and BoNT-A to the hindpaw skin of Sprague-Dawley rats results in a significant reduction in plasma extravasation evoked by electrical stimulation, also but less in plasma extravasation evoked by capsaicin. Subcutaneous administration of BoNT-A also reduces vasodilation caused by saphenous nerve stimulation. BoNT-A does not interfere with substance P- and calcitonin gene-related peptide-induced vasodilation
additional information
-
the toxin persists in neuronal cells for an extended period, it maintaines its ability to cleave VAMP2 in human neuronal cells for weeks
additional information
the translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A
additional information
-
the translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A
additional information
-
uptake of BoNT/A, B, E and G into cells requires a dual interaction with gangliosides and the synaptic vesicle proteins synaptotagmin or SV2. Interaction of SV2A, SV2B and SV2C with botulinum neurotoxin F HC, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
102000
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
104000
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
146000
recombinant His-tagged BoNT AE and EA chimeras, gel filtration
146900
-
Clostridium botulinum, serotype BoNT/D, calculated from nucleotide sequence
148700
-
Clostridium botulinum, serotype BoNT/C1, calculated from nucleotide sequence
149400
-
Clostridium botulinum, serotype BoNT/A, calculated from nucleotide sequence
149500
-
Clostridium botulinum, serotype BoNT/A, calculated from nucleotide sequence
150000
152000
-
Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence
155000
-
Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence
50000
51000
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
53000
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
60000
-
7 * 60000, activated C2II binding component, which oligomerizes into heptamers and forms channels in lipid bilayer membranes, residues 303-330 of C2II contain a conserved pattern of alternating hydrophobic and hydrophilic residues, which is involved in the formation of two amphipathic beta-strands involved in membrane insertion and channel formation
97000
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
additional information
100000
1 * 50000 + 1 * 100000, light chain and heavy chain yielded by posttranslational modification by bacterial or exogenous proteases
100000
-
1 * 50000 + 1 * 100000, light chain LC and heavy chain HC, linked by a disulfide bridge
100000
-
1 * 50000 + 1 * 100000, light chain and heavy chain, covalently linked by a disulfide bond
100000
P10845
1 * 50000, light chain, + 1 * 100000, heavy chain, linked by a disulfide bond
150000
-
Clostridium botulinum, serotype BoNT/A, SDS-PAGE, calculated from amino acid sequence
50000
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
50000
1 * 50000 + 1 * 100000, light chain and heavy chain yielded by posttranslational modification by bacterial or exogenous proteases
50000
-
1 * 50000 + 1 * 100000, light chain LC and heavy chain HC, linked by a disulfide bridge
50000
-
1 * 50000 + 1 * 100000, light chain and heavy chain, covalently linked by a disulfide bond
50000
P10845
1 * 50000, light chain, + 1 * 100000, heavy chain, linked by a disulfide bond
50000
P10845
x * 50000, type A botulinum neurotoxin light chain, SDS-PAGE
additional information
-
comparison of amino acid sequences of H- and L-chains of serotypes A, B and E
additional information
-
comparison of amino acid sequences of botulinum serotype BoNT/A and tetanus neurotoxin
additional information
-
comparison of amino acid sequences of botulinum serotype BoNT/A and tetanus neurotoxin
additional information
-
analytical gel filtration analysis of enzyme fragments from trypsin-derived nicks in the enzyme molecule, overview
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 50000, light chain subunit of botulinum neurotoxin B, SDS-PAGE
dimer
heptamer
-
7 * 60000, activated C2II binding component, which oligomerizes into heptamers and forms channels in lipid bilayer membranes, residues 303-330 of C2II contain a conserved pattern of alternating hydrophobic and hydrophilic residues, which is involved in the formation of two amphipathic beta-strands involved in membrane insertion and channel formation
heterodimer
oligomer
oligomerization of BoNT/E is dependent only on GT1b and does not require low pH
additional information
?
x * 146000, recombinant His-tagged BoNT AE and EA chimeras, SDS-PAGE
?
-
x * 52200, light chain subunit of botulinum neurotoxin type A, SDS-PAGE
dimer
-
1 * 50000 + 1 * 102000, Clostridium botulinum, serotype BoNT/E, calculated from amino acid sequence, 1 * 51000 + 1 * 104000, Clostridium botulinum, serotype BoNT/B, calculated from amino acid sequence, 1 * 53000 + 1 * 97000, Clostridium botulinum, serotype BoNT/A, calculated from amino acid sequence
dimer
1 * 50000 + 1 * 100000, light chain and heavy chain yielded by posttranslational modification by bacterial or exogenous proteases
dimer
-
1 * 50000 + 1 * 100000, light chain LC and heavy chain HC, linked by a disulfide bridge
dimer
-
1 * 50000 + 1 * 100000, light chain and heavy chain, covalently linked by a disulfide bond
dimer
P10845
1 * 50000, light chain, + 1 * 100000, heavy chain, linked by a disulfide bond
heterodimer
1 * about 100000 + 1 * about 60000, subtype BoNT/F7, SDS-PAGE
heterodimer
1 * about 100000 + 1 * about 70000, subtype BoNT/F5, SDS-PAGE
additional information
enzyme model with light chain LC or effector domain, showing the catalytic activity, heavy chain HC binding domain binding to neuronal receptors, after which the HN translocation domain mediates the entry of the light chain into the nerve cell
additional information
P10845
enzyme model with light chain LC or effector domain, showing the catalytic activity, heavy chain HC binding domain binding to neuronal receptors, after which the HN translocation domain mediates the entry of the light chain into the nerve cell
additional information
-
synthesized as single-chain polypeptide of about MW 150000 Da, proteolytic activation yields 2-chain neurotoxin with N-terminal light (MW 50000 Da) and C-terminal heavy chains (MW 100000 Da) connected by single disulfide bonds
additional information
-
synthesized as single-chain polypeptide of about MW 150000 Da, proteolytic activation yields 2-chain neurotoxin with N-terminal light (MW 50000 Da) and C-terminal heavy chains (MW 100000 Da) connected by single disulfide bonds
additional information
-
synthesized as single-chain polypeptide of about MW 150000 Da, proteolytic activation yields 2-chain neurotoxin with N-terminal light (MW 50000 Da) and C-terminal heavy chains (MW 100000 Da) connected by single disulfide bonds
additional information
-
serotype BoNT/E: single-chain polypeptide, serotype BoNT/B: mixture of single- and 2-chain molecules, serotype BoNT/A: 2-chain molecule
additional information
-
Clostridium botulinum C2 toxin is a binary AB type toxin that is structurally organized into distinct enzyme and binding components, i.e. A and C2I components and B and C2II components, respectively
additional information
-
comparison of wild-type and mutant tertiary structure by circular dichroism, overview
additional information
near-complete conversion of the SC to a disulfide-linked DCas revealed by the appearance of the HC and LC upon SDS-PAGE in the presence of DTT
additional information
-
the enzyme is a binary toxin, which is composed of two separate proteins, the enzyme component C2I and the component C2IIa, overview
additional information
-
BoNT is a 150 kDa protein consisting of a 100 kDa heavy-chain, Hc, and a 50 kDa light-chain, Lc. Epitope mapping of the light chain, overview
additional information
-
BoNT is a modular enzyme of trimodular protein architecture with an N-terminal Zn2+-metalloprotease, which cleaves the SNARE substrate and chaperones the protease across endosomes, and a C-terminal receptor binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis, overview. The activated mature toxin consists of the three modules: the N-terminal LC Zn2+-metalloprotease, the heavy chain that encompasses the N-terminal translocation domain HN, and the C-terminal receptor-binding domain HC. The latter comprises two subdomains, a beta-sheet jelly roll fold, denoted HCN, and a beta-tree foil fold carboxy subdomain, known as HCC, structure, overview
additional information
-
BoNT/A is composed of a heavy (HC) and light (LC) chain linked by a disulfide bond
additional information
BoNTs are large neurotoxic proteins of about 150 kDa that consist of a light chain of 50 kDa, and a heavy chain of 100 kDa linked by a disulfide bond. BoNTs possess binding, translocation and catalytic domains
additional information
-
BoNTs are large neurotoxic proteins of about 150 kDa that consist of a light chain of 50 kDa, and a heavy chain of 100 kDa linked by a disulfide bond. BoNTs possess binding, translocation and catalytic domains
additional information
-
BoNTs are proteins comprised of three functional domains, the light chains, LCs, the heavy chain, HC, and the translocation HN of the LC into the cell cytoplasm
additional information
-
BoNTs are synthesized as150-kDa proteins consisting of a 100-kDa heavy chain, HC, and a 50-kDa light chain, LC, linked by disulfide bonds
additional information
-
BoNTs consist of a light chain of 50 kDa and a heavy chain of 100 kDa
additional information
-
each BoNT serotype consists of a heavy chain, HC, of 100 kDa covalently attached by a disulfide bond to a light chain, LC, of 50 kDa
additional information
-
each toxin is composed of a heavy, HC, 100 kDa, and a light chain, L, 50 kDa, linked by a disulfide bond and non-covalent interactions
additional information
enzyme model with light chain LC or effector domain, showing the catalytic activity, heavy chain HC binding domain binding to neuronal receptors, after which the HN translocation domain mediates the entry of the light chain into the nerve cell
additional information
P10845
enzyme model with light chain LC or effector domain, showing the catalytic activity, heavy chain HC binding domain binding to neuronal receptors, after which the HN translocation domain mediates the entry of the light chain into the nerve cell
additional information
in BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Separation of the domains causes conformational changes. Domain organization of BoNT E, modelling, overview
additional information
-
in BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Separation of the domains causes conformational changes. Domain organization of BoNT E, modelling, overview
additional information
-
localization of the antigenic regions on the heavy chains of BoNTs A and B, epitope mapping, overview. Mapping of the regions on BoNTs A and B that bind blocking antibodies in hyperimmune sera against the correlated toxin from human, mouse and other species, submolecular specificity of blocking antibodies that appear in humans, profile and threedimensional structure, overview
additional information
structure comparisons of BoNT/G HCR, BoNT/A HCR, and BoNT/B HCR, modelling, overview
additional information
-
the BoNT HC-LC subunits are held together by a single disulfide bond
additional information
-
the BoNT toxin is composed of a catalytic light chain, a heavy chain, and a translocation domain
additional information
-
the transmembrane domain comprises residues A449 to I873, and the receptor binding domain residues I874 to L1296. Epitope tagging by specific antibodies, recombinant peptide fragment binding experiments, the epitopes for antibodies F1-2 and F1-5 are located between amino acids R564 and S793 on the toxin heavy chain, overview
additional information
-
three-dimensional structure of BoNT showing the catalytic, translocation, and receptor-binding domains, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
additional information
-
BoNT/B LC is processed for removal via the proteasome-dependent degradation pathway after ubiquitination in neuronal cells
proteolytic modification
-
BoNT/A LC undergoes autocatalytic degradation into two major fragments in the presence of exogenous zinc, autolysis of wild-type and mtant BoNT/As, overview
proteolytic modification
P10845
BoNTs are produced as a single 150 kDa polypeptide chain that is subsequently cleaved by endogenous proteases to give the dichain holotoxin
proteolytic modification
-
limited trypsin proteolysis of BoNT produces two nicks, the first nick yields a BoNT 50 kDa light chain disulfide linked to a 100 kDa heavy chain, a second nick arose in Hc C-terminal 10 kDa. The second nick occurrs in the putative binding domain of the BoNT molecule and induces alterations in its secondary structure, leading to a significant reduction of mouse toxicity in comparison with that of the fully activated singly nicked BoNT
proteolytic modification
-
the C2II binding enzyme component is proteolytically activated
proteolytic modification
-
BoNTs are synthesized as single inactive polypeptide chains that are cleaved by endogenous or exogenous proteases to generate the active dichain form of the toxin. Nicking of the single chain BoNT/E to the dichain form is associated with 100fold increase in toxicity
proteolytic modification
-
the inactive precursor protein is cleaved either by clostridial or tissue proteases into a 50-kDa light chain and a 100 kDa heavy chain linked by an essential interchain disulfide bridge and by the belt, a loop from the heavy chain that wraps around the light chain. Intracellular processing of the toxin, importance of unfolding for efficient translocation, detailed overview
proteolytic modification
-
the toxins are synthesized as single polypeptide chains containing both heavy chain and light chain that are activated after undergoing posttranslational proteolysis
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
binding domain of subtype BoNT/, sitting drop vapor diffusion method, using 10 mM spermine tetrahydrochloride, 10 mM spermidine trihydrochloride, 10 mM 1,4-diaminobutane dihydrochloride, 10 mM DL-ornithine monohydrochloride, 0.1 M MOPSO/bis-Tris pH 6.5, 15% (w/v) PEG 3 K, 20% (w/v), 1,2,4-butanetriol, 1% (w/v) NDSB 256
binding domain of subtype BoNT/A4, sitting drop vapor diffusion method, using 10 mM spermine tetrahydrochloride, 10 mM spermidine trihydrochloride, 10 mM 1,4-diaminobutane dihydrochloride, 10 mM DL-ornithine monohydrochloride, 0.1 M MOPSO/bis-Tris pH 6.5, 15% (w/v) PEG 3 K, 20% (w/v), 1,2,4-butanetriol, 1% (w/v) NDSB 256
BoNT E holotoxin, sitting-drop vapor diffusion, 8 mg/ml toxin in 50 mM HEPES buffer and 100 mM NaCl at pH 7.0, is mixed in a 1:1 ratio with reservoir solution containing 10% PEG 8000, 100 mM NaCl, and 100 mM HEPES at pH 7.0 at 18 °C, crystals appear after 1 weeks and grow to full-size within 2 weeks, X-ray diffraction structure determination and analysis at 2.65 A resolution
BoNT/F in complex with inhibitors VAMP 22-58/Gln58D-cysteine and VAMP 27-58/Gln58D-cysteine, X-ray diffraction structure determination and analysis at 2.1 A and 2.17 A resolution, respectively
botulinum neurotoxin A-receptor-binding domain in complex with the SV2C luminal domain, vapor diffusion method, using 100 mM HEPES, pH 7.5, 6% (w/v) PEG 8000, 8% (v/v) glycerol and 100 mM NaCl
P10845
botulinum neurotoxin E light chain, sitting drop vapor diffusion method
-
catalytic and translocation domain of botulinum neurotoxin type D, sitting drop vapor diffusion method, using 0.1 M sodium actetate pH 5.5, 0.8 M sodium formate, 10% (w/v) polyethylene glycol 8000, 10% (w/v) polyethylene glycol 1000
complex between the botulinum neurotoxin A light chain and the inhibitory peptide N-Ac-CRATKML, X-ray diffraction structure determination and analysis at 1.4 A resolution, and in a second approach unliganded enzyme light chain with and without the Zn2+ cofactor bound, X-ray diffraction structure determination and anaylsis at 1.25 A and 1.20 A resolution, respectively, 6-8 mg/ml purified BoNT/ALC, residues 1-425, in 50 mM NaPO4, pH 6.0, and 2 mM EDTA, hanging drop vapor diffusion method, mixing of protein solution with reservoir solution containing 20% PEG 3,350, 0.2 M diammonium tartrate, pH 6.6, and equilibration against 0.5 ml reservoir solution, the crystals are soaked prior to cryo-cooling in the crystallization solution plus 10 mM Zn(NO3)2 for 4.5 h or 5 mM Zn(NO3)2 and 2 mM N-Ac-CRATKML for 23 h, respectively, modeling
P10845
complex of botulinum neurotoxin serotype A protease bound to human SNAP-25, 2.1 A resolution
-
crystal structure of BoNT/CD-HCR (S867-E1280) is determined at 1.56 A resolution and compared to previously reported structures for BoNT/DHCR. The BoNT/CD-HCR structure is similar to the two sub-domain organization observed for other BoNT HCRs: an N-terminal jellyroll barrel motif and a C-terminal beta-trefoil fold
full length Clostridium botulinum neurotoxin type E light chain, sitting drop vapor diffusion method, crystals diffract to better than 2.1 A, crystals belong to space group P2(1)2(1)2 with cell dimensions a = 88.33 A, b = 144.45 A, c = 83.37 A
-
hanging drop vapor diffusion at 22°C, crystal structure of Clostridium botulinum neurotoxin protease in a product-bound state
-
hanging drop vapor diffusion method, using either 19% (w/v) PEG1500, 0.1 M MMT pH 6.0 or 11% (w/v) PEG20000, 0.1 M MES pH 6.5, 10 mM EDTA
hemagglutinin 33 component of botulinum neurotoxin type B progenitor toxin complex bound to lactose, hanging drop vapor diffusion method, using 0.1 M HEPES (pH 7.0), 5% MPD, 5% (w/v) PEG [poly(ethylene glycol)] 6k, and 20 mM lactose
-
high-resolution structure of botulinum neurotoxin serotype F light chain in two crystal forms, sitting drop vapor diffusion method
-
in complex with non-toxic non-hemagglutinin protein, small-angle X-ray scattering
P10845
light chain protease domain of botulinum neurotoxin type HA, hanging drop vapor diffusion method, using 100 mM calcium acetate, 100 mM sodium cacodylate, pH 5.5 and 4% (w/v) polyethylene glycol 8000
-
mutant enzyme E1191M/S1199Y in complex with synaptotagmin 1, sitting drop vapor diffusion method, using 1.1 M sodium malonate dibasic monohydrate, HEPES (pH 7.0), and 0.5% (v/v) Jeffamine ED-2003. Mutant enzyme E1191M/S1199Y in complex with synaptotagmin 2, sitting drop vapor diffusion method, using 0.2 M MgCl2, Tris (pH 7.0), and 10% (w/v) PEG 8000
-
nanodroplet vapor diffusion method, 1.65 A resolution crystal structure of the catalytic domain of BoNT serotype D light chain. Structural analysis has identified a hydrophobic pocket potentially involved in substrate recognition of the P1' VAMP residue (Leu 60) and a second remote site for recognition of the V1 SNARE motif that is critical for activity. A structural comparison of BoNT/D-LC with BoNT/F-LC that also recognizes VAMP-2 one residue away from the BoNT/D-LC site provides additional molecular details about the unique serotype specific activities. In particular, BoNT/D prefers a hydrophobic interaction for the V1 motif of VAMP-2, while BoNT/F adopts a more hydrophilic strategy for recognition of the same V1 motif
-
nanodroplet vapor diffusion method, crystal structure of botulinum neurotoxin type G light chain at 2.35 A resolution
-
purified recombinant enzyme free or in complex with substrate analogue inhibitor peptides, sitting drop vapor diffusion method at room temperature, 0.002 ml of 20 mg/ml enzyme in 2 mM DTT, 200 mM NaCl, and 20 mM HEPES, pH 7.4, is mixed with 0.002 ml reservoir solution containing 15% w/v PEG 3350, 0.3 M ammonium sulfate and 100 mM Bis-Tris buffer, pH 6.8 , equilibration against 0.8 ml of reservoir solution, plate-like crystals within a week, recombinant Balc424 is co-crystallized individually with the tetrapeptides, sitting drop vapor diffusion method at room temperature using conditions similar to native protein, Balc424 gives good complex crystals with RRGC, RRGM, RRGL and RRGI at stoichiometric ratios of 1:30, 1:30, 1:40 and 1:40, respectively, X-ray diffraction structure determination and analysis at 1.6-1.8 A resolution
P10845
purified recombinant His-tagged BoNT/C1-LC, vapour diffusion method, 12 mg/ml protein in 20 mM HEPES, pH 7.4, is mixed with an equal volume of reservoir solution containing 1.6 M sodium formate and 0.1 M sodium citrate, pH 4.6-5.0, 4°C, cryoprotection in the same mother liquor supplemented with 20% glycerol, X-ray structure determination and analysis at 1.75 A resolution, molecular replacement
-
purified recombinant His-tagged BoNT/G HCR, hanging drop vapour diffusion method, 11.5 mg/mL protein in mother liquor containing 12-15% w/v PEG 3350, 20 mM Bis-Tris buffer, pH 5.75-6.5, and 20-25 mM MgCl, X-ray diffraction structure determination and analysis at 2.0 A resolution, modelling
purified recombinant His-tagged truncated enzyme, residues 1-424, in complex with inhibitors 4-chlorocinnamic hydroxamate, 2,4-dichlorocinnamic hydroxamate, and L-arginine hydroxamate, hanging drop vapor diffusion method, drops are formed of equal parts BoNT/A-LC(1-424) at 10 mg/ml in 20 mM HEPES, pH 7.5, 50 mM NaCl and well solution containing 10%-15% PEG-2000 monomethyl ether, 0.3M(NH4)2HPO4, 50 mM Tris, pH 8.5, co-crystallization with inhibitor by addition of 0.5 mM ligand to the protein solution, 1.3 days, larger crystals by microseeding, X-ray diffraction structure determination and analysis at 1.9-2.5 A resolution, modeling
-
purified recombinant native and SeMet-derivative enzyme, mixing of 0.001 ml protein solution containing 1 mg/ml protein in 20 mM Tris-HCl, pH 8.0, and 200 mM NaCl, with 0.001 ml reservoir buffer, containing 0.2 M potassium/sodium tartrate, 0.1 M trisodium citrate, pH 5.6, and 1 M ammonium sulfate for the native enzyme, and 0.1 M MES pH 6.5, 1.6 M magnesium sulfate, and 1 M sodium chloride for the selenium methionine-labeled enzyme, equilibration against 0.1 ml reservoir buffer, 20°C, X-ray diffraction structure determination and analysis at 2.8 A and 3.1 A resolution, respectively
purified recombinant protein consisting of the receptor-binding domain of botulinum neurotoxin serotype B fused to the luminal domain of synaptotagmin II, vapour diffusion method, 20°C, using first 13% PEG 6000 and 0.1 M HEPES pH 7.0, and second, 0.8 M sodium citrate, pH 6.5, X-ray diffraction structure detremination and analysis at 2.15 A resolution, molecular replacement and modeling
-
subtype BoNT/B bound to both its protein receptor and ganglioside 1a, vapor diffusion method, using 0.2 M MgCl2, 0.1M HEPES pH 7.0-7.2 and 20-24% (w/v) PEG 6000
subtype BoNT/CD-heavy chain receptor binding domain, hanging drop vapor diffusion method, using 1.6 M (NH4)2SO4, 2% (w/v) PEG 400, and 0.1 M HEPES, pH 7.5
the crystal structure of the BoNT/F receptor-binding domain in complex with the sugar moiety of ganglioside GD1a is reported. GD1a binds in a shallow groove formed by a conserved peptide motif, with additional stabilizing interactions provided by two arginine residues
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D877N
the mutant shows 20% reduced neurotoxicity compared to the wild type
E48Q
the mutant shows 64% reduced neurotoxicity compared to the wild type
E48Q/D877N
the mutant shows 8% increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain
E48Q/E653K
the mutant shows 9% reduced neurotoxicity compared to the wild type
E48Q/E653Q
the mutant shows 38% reduced neurotoxicity compared to the wild type
E48Q/E653Q/D877N
the mutant shows 54% increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain
E653 K/D877N
the mutant shows 28% increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain
E653K
the mutant shows 15% reduced neurotoxicity compared to the wild type
E653Q
the mutant shows 31% reduced neurotoxicity compared to the wild type
E653Q/D877N
the mutant shows 32% increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain
C134A
-
site-directed mutagenesis, mutation of a binding site residue, the mutant shows reduced activity compared to the wild-type enzyme
C461S
the mutant shows similar levels of activity as the wild type enzyme
C467S
the mutant shows similar levels of activity as the wild type enzyme
D130A
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
D341A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
D342C
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
D369N
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
D370A
-
site-directed mutagenesis, mutation of an S1' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
D370R
-
site-directed mutagenesis, mutation of an S1' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
D426A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
E1172A
-
the binding of radioactively-labeled, in vitro translated HCE E1172A to rat brain synaptosomes is highly decreased to 8.5% of wild-type levels, as well as the binding of Escherichia coli derived HCE mutants to isolated GT1b
E1191C/S1199W
-
the mutations enhance enzyme binding to human synaptotagmin II and human synaptotagmin I
E1191M/S1199Y
E1191Q/S1199W
-
the mutation enhances binding to the human receptor synaptotagmin 2
E1191V/S1199W
-
the mutations enhance enzyme binding to human synaptotagmin II and human synaptotagmin I
E1195A
-
the HCF mutant E1195A displays a diminished affinity of 31.6% to synaptosomes as well as a reduction of about 85% in binding to isolated GT1b compared to HCF wild-type
E147A/E308A
-
the mutant exhibits a 5fold reduction of wild type activity
E158A/T159A/N160A
-
kcat/KM for synaptosome-associated protein SNAP-25 is 7.4fold lower than the wild-type value
E163L
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
E163Q
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
E170A
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
E200A
-
Km (VAMP-2) similar to wild-type, kcat strongly decreased compared to wild-type
E212A/E335Q
-
no detectable activity with synaptosome-associated protein SNAP-25
E224A
-
the mutation abrogates the catalytic activity of the endopeptidase of BoNT/A
E224A/E262A
-
the recombinant full length botulinum type A with mutation in its two active site residues is a detoxified BoNT/A mutant since it lacks its endopeptidase activity
E224D
-
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
E249A
-
kcat/KM for synaptosome-associated protein SNAP-25 is 20fold lower than the wild-type value
E256A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme in addition of ZnCl2 but not in absence of it, the ratio of activity in absence or presence of exogenous ZnCl2 is altered compared to the wild-type enzyme
E257A
-
site-directed mutagenesis, mutation of an S4' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
E257K
-
site-directed mutagenesis, mutation of an S4' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
E262D
-
site-directed mutagenesis, the mutant shows a three-fold reduced activity compared to the wild-type enzyme
E262Q
-
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
E272A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
E280C
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
E315A
-
Km (VAMP-2) increased compared to wild-type, kcat similar to wild-type
E335A
-
kcat/KM for synaptosome-associated protein SNAP-25 is 37fold lower than the wild-type value
E335Q
-
kcat/KM for synaptosome-associated protein SNAP-25 is 7300fold lower than the wild-type value. Mutation causes the toxin to transform into a persistent apoenzyme decoid of zinc
E346A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
E399/D426A/F428A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows almost no channel forming activity
E399A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows unaltered channel forming activity compared to the wild-type enzyme
E399A/D425A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows almost no channel forming activity
E54A
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
E63A
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
F163A
-
site-directed mutagenesis, mutation of an S1' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
F194A
-
site-directed mutagenesis, mutation of an S1' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
F194A/T220A
-
site-directed mutagenesis, mutation of S1' pocket residues, the mutant shows reduced activity compared to the wild-type enzyme
F428A
-
site-directed mutagenesis, a C2II component mutant, the mutant shows altered chloroquine binding and almost no channel formation activity compared to the wild-type enzyme
F428D
-
site-directed mutagenesis, a C2II component mutant, the mutant shows altered chloroquine binding and almost no channel formation activity compared to the wild-type enzyme
F428W
-
site-directed mutagenesis, a C2II component mutant, the mutant shows altered chloroquine binding and almost no channel formation activity compared to the wild-type enzyme
F428Y
-
site-directed mutagenesis, a C2II component mutant, the mutant shows altered chloroquine binding and almost no channel formation activity compared to the wild-type enzyme
F50A/I191A
the mutant shows 60fold activity reduction compared to the wild type enzyme
F50D
the mutant shows 4fold activity reduction compared to the wild type enzyme
F50D/I191D
the mutant shows 400fold activity reduction compared to the wild type enzyme
H1241K
mutant shows an increased affinity for GD1a and confers the ability to bind ganglioside GM1a
H132Q
the mutant shows 100fold activity reduction compared to the wild type enzyme
H223A
-
the mutation abrogates the catalytic activity of the endopeptidase of BoNT/A
H223A/E224A/H227A
-
site-directed mutagenesis of active site residues, catalytically inactive BoNT/A1 mutant
H227A
-
the mutation abrogates the catalytic activity of the endopeptidase of BoNT/A
H269A
-
site-directed mutagenesis, the mutant shows unaltered activity compared to the wild-type enzyme
I115A
-
site-directed mutagenesis, mutation of a binding site residue, the mutant shows reduced activity compared to the wild-type enzyme
I151A
the mutant shows 2fold activity reduction compared to the wild type enzyme
I151D
the mutant shows 1000fold activity reduction compared to the wild type enzyme
I152D
the mutant shows 2fold activity reduction compared to the wild type enzyme
I191D
the mutant shows 4fold activity reduction compared to the wild type enzyme
I52A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
K165L
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
K172A
-
Km (VAMP-2) increased compared to wild-type, kcat moderately decreased compared to wild-type
K224D
-
mutation of BoNT/E light chain. The mutant shows extended substrate specificity to cleave SNAP-23, and the natural substrate, SNAP-25, but not SNAP-29 or SNAP-47, introduction into HeLa cells
K29A
the BoNT F K29A mutation does not abrogate VAMP cleavability
K41A
-
site-directed mutagenesis, mutation of a binding site residue, the mutant shows reduced activity compared to the wild-type enzyme
L173A
-
Km (VAMP-2) increased compared to wild-type, kcat moderately decreased compared to wild-type
L175A
-
site-directed mutagenesis, mutation of an S5 pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
L175A/R177A
-
site-directed mutagenesis, mutation of S5 pocket residues, the mutant shows reduced activity compared to the wild-type enzyme
L200A
the mutant shows 2fold activity reduction compared to the wild type enzyme
L200D
the mutant shows 8fold activity reduction compared to the wild type enzyme
L256E/V258P
-
the mutant shows 49.3% of wild type SNAP-25 cleavage activity
P154D
the mutant shows 4fold activity reduction compared to the wild type enzyme
P25A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
Q138G/P139G/D140G
-
site-directed mutagenesis, the mutant is no longer recognized by antibody F1-40
Q161A
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
Q162A
Q34A
-
the mutation reduces the VAMP-2 cleavability by about 3fold compared to the wild type enzyme
Q66A
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
R1111A/H1241K/R1256A
triple mutant binds GD1a 17fold greater than the double-mutant
R1111A/R1256A
triple mutant binds GD1a 17fold greater than the double-mutant
R133A
R133K
the BoNT/F mutant shows over 95% reduced activity with VAMP substrate compared to the wild-type enzyme
R171A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
R171K
the exosite 1 variant BoNT F shows about 98% reduction in activity with VAMP compared to the wild-type enzyme
R177A
R230K
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
R230L
R23D/H132A
the mutant shows 25fold activity reduction compared to the wild type enzyme
R240A
-
Km (VAMP-2) similar to wild-type, kcat decreased compared to wild-type
R263A
-
Km (VAMP-2) similar to wild-type, kcat decreased compared to wild-type
R347A
-
kcat/KM for synaptosome-associated protein SNAP-25 is 1060fold lower than the wild-type value
R362L
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
R372A
the mutant shows 40fold activity reduction compared to the wild type enzyme
R63A
the mutant shows 10fold activity reduction compared to the wild type enzyme
R63E
the mutant shows 50fold activity reduction compared to the wild type enzyme
S147A
-
Km (VAMP-2) increased compared to wild-type, kcat similar to wild-type
S224A
-
Km (VAMP-2) similar to wild-type, kcat decreased compared to wild-type
S28E
-
the mutation reduces the VAMP-2 cleavability by about 2fold compared to the wild type enzyme
T176A
-
site-directed mutagenesis, mutation of an S5 pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
T220A
-
site-directed mutagenesis, mutation of an S1' pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
V129A
-
site-directed mutagenesis, mutation of a binding site residue, the mutant shows reduced activity compared to the wild-type enzyme
V137A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
V148/I151A
the mutant shows 15fold activity reduction compared to the wild type enzyme
W1224L
-
the binding of radioactively-labeled, in vitro translated HCE W1224L to rat brain synaptosomes is highly decreased to 3.7% of wild-type levels, as well as the binding of Escherichia coli derived HCE mutants to isolated GT1b
W1250L
-
the HCF mutant W1250L displays a diminished affinity of 20.5% to synaptosomes as well as a reduction of about 85% in binding to isolated GT1b compared to HCF wild-type
W1266L
-
the mutant HCA W1266L that lacks ganglioside binding, does not interfere with BoNT/A neurotoxicity
W315A
the mutant shows 20fold activity reduction compared to the wild type enzyme
W315D
the mutant shows 40fold activity reduction compared to the wild type enzyme
W319A
-
Km (VAMP-2) increased compared to wild-type, kcat similar to wild-type
W44A
-
Km (VAMP-2) increased compared to wild-type, kcat similar to wild-type
W44A/I152A/P154A
the mutant shows 20fold activity reduction compared to the wild type enzyme
W44D
the mutant shows 2fold activity reduction compared to the wild type enzyme
Y113A
-
Km (VAMP-2) increased compared to wild-type, kcat similar to wild-type
Y133A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
Y168A
Y168A/L200A
the mutant shows 2fold activity reduction compared to the wild type enzyme
Y168D
the mutant shows 2fold activity reduction compared to the wild type enzyme
Y168D/L200D
the mutant shows 60fold activity reduction compared to the wild type enzyme
Y183A/Y239A
-
the mutant exhibits a 1000fold reduction of wild type activity
Y26A
Y26A/Y50A/T192A
-
the mutant exhibits a 600fold reduction of wild type activity
Y322A
-
Km (VAMP-2) increased compared to wild-type, kcat similar to wild-type
Y350A
-
no detectable activity with synaptosome-associated protein SNAP-25
Y361A
the BoNT/F mutant shows about 18% reduction in activity with VAMP compared to the wild-type enzyme
Y365F
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y365N
Y368A
-
Km (VAMP-2) similar to wild-type, kcat strongly decreased compared to wild-type
additional information
E1191M/S1199Y
-
the mutant exhibits about 11fold higher efficacy in blocking neurotransmission than wild type botulinum neurotoxin B in neurons expressing human synaptotagmin II
E1191M/S1199Y
-
the mutation enhances binding to the human receptor synaptotagmin 2
Q162A
-
site-directed mutagenesis, the mutant shows unaltered activity compared to the wild-type enzyme
R133A
the BoNT/F mutant shows over 95% reduced activity with VAMP substrate compared to the wild-type enzyme
R177A
-
site-directed mutagenesis, mutation of an S5 pocket residue, the mutant shows reduced activity compared to the wild-type enzyme
R230L
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
Y168A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
Y26A
-
Km (VAMP-2) increased compared to wild-type, kcat decreased compared to wild-type
Y365N
-
site-directed mutagenesis, the mutant shows reduced activity and an altered ratio of activity in absence or presence of exogenous ZnCl2 compared to the wild-type enzyme
additional information
-
an insertion mutant moving Glu224 laterally by one residue is catalytically inactive
additional information
-
construction and growth-selection of chimeric SNARE mutations that inhibit proteolysis, when these mutations are introduced into Sb and examined for cleavage, substrate residues located near and distal to the cleavage site are important, including residues positioned near the Sb transmembrane domain, overview, additional mutations in a nine-residue SNARE motif
additional information
-
construction of a HCB-Syt-II fusion protein by fusion of the HC fragment of BoNT/B, residues 858-1291, with the luminal domain of rat Syt-II, residues 861, connected by a 15-residue linker, PPTPGSAWSHPQFEK, including a Strep-tag, site-directed mutagenesis analysis of the toxin-receptor binding site in BoNT/B and in the luminal domains of Syt-I and Syt-II, overview
additional information
construction of BoNT AE and EA chimeras from serotypes BoNT/A and BoNT/E in DC and SC forms, overview, catalytic and physiological properties of the chimeric forms, overview
additional information
-
an atoxic derivative of BoNT/A (BoNT/A ad) as a full-length 150 kDa molecule consisting of a 50 kDa light chain and a 100 kDa heavy chain joined by a disulfide bond and metalloprotease-inactivating point mutations (E224A/Y366A) in the light chain. Studies in neuronal cultures demonstrates that the mutant is unable to cleave SNAP25, and that it effectively competes with wild-type BoNT/A for binding to endogenous neuronal receptors. In vivo studies indicate accumulation of the mutant (BoNT/A ad) at the neuromuscular junction of the mouse diaphragm. Toxicity of the mutant BoNT/A ad is reduced by 100000fold relative to wild-type BoNT/A
additional information
-
an atoxic derivative of BoNT/A (BoNT/A ad) as a full-length 150 kDa molecule consisting of a 50 kDa light chain and a 100 kDa heavy chain joined by a disulfide bond and metalloprotease-inactivating point mutations (E224A/Y366A) in the light chain. Studies in neuronal cultures demonstrates that the mutant is unable to cleave SNAP25, and that it effectively competes with wild-type BoNT/A for binding to endogenous neuronal receptors. In vivo studies indicate accumulation of the mutant (BoNT/A ad) at the neuromuscular junction of the mouse diaphragm. Toxicity of the mutant BoNT/A ad is reduced by 100000fold relative to wild-type BoNT/A
additional information
-
four variants of type A BoNT (BoNT/A) light chain are prepared and their catalytic parameters with those of BoNT/A whole toxin are compared. The four variants are light chain + translocation domain, a trypsin-nicked light chain + translocation domain, light chain + belt, and a free light chain. Km (SNAP-25) (synaptosomal associated protein of 25 kDa) for these constructs is not very different, but kcat for the free light chain is 6-100fold higher than those of its four variants. None of the four variants of the light chain is prone to autocatalysis
additional information
-
the endopeptidase activities of the three forms (complex, purified BoNT/B holotoxin, and separated light chain) are compared under the same conditions. Results show that enzyme activities of the three forms differ significantly and are dependent on nicking and disulfide reduction conditions. Light chain form has the highest level of activity, and the complex has the lowest. The activity is enhanced by nicking of BoNT/B holotoxin and is enhanced even more by dithiothreitol reduction after nicking
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
the BoNT complex and its components precipitate below pH 5.5, overview
710875
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
38 - 41
-
thermal denaturation of wild-type and mutant BoNT/As, overview
44
44 - 52
-
temperature denaturation Tm is significantly decreased upon removal of Zn2+
51 - 60
the melting temperature is around 51°C at pH 7.2 and 60.4°C at pH 4.5
additional information
-
thermodynamic parameters for temperature-induced denaturation of BoNT/E, overview
44
-
BoNT/A activity significantly decreases after 30 min incubation and is not detected at 3 h or longer incubation time
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
BoNT/A is sensitive to proteolysis at 44°C. Only EDTA and EDTA (1 mM) block degradation
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Glycerol
secondary and tertiary structures are substantially stabilized by the presence of 10-50% (v/v) glycerol
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, in 10 mM HEPES buffer, pH 7.2, 50 mM NaCl, after freezing in liquid N2, stable
-
the recombinant enzyme is most stable stored at pH 4.0 in 15 mM succinate
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native BoNT/A1, BoNT/A3, BoNT/B1, and BoNT/B4 from strains ATCC 3502, NCTC 2012, Okra, and Eklund 17B strains, respectively, by ultrafiltration, hydrophobic interaction and anion exchange chromatography, followed by hydroxyapatite chromatography and dialysis
P10844, P10845
native BoNT/B1, and BoNT/B4 by ultrafiltration, hydrophobic interaction and anion exchange chromatography, followed by hydroxyapatite chromatography and dialysis
P10844, P10845
ammonium sulfate precipitation, DEAE column chromatography, and 4-aminobenzyl 1-thio-beta-D-galactopyranoside agarose affinity column chromatography
-
ammonium sulfate precipitation, DEAE column chromatography, CM Sepharose column chromatography, and Mono-Q column chromatography
ammonium sulfate precipitation, Ni-NTA agarose column chromatography, and DEAE-Sephadex gel filtration
-
BoNT HCR/A and HCR/B co-purify with synaptic vesicle protein complexes
-
BoNT serotype D and enzyme large toxin complex, L-TC, from strain 4947, by ammonium sulfate fractionation, cation exchange chromatography, another step of ammonium sulfate fractionation, and gel filtration
-
BuHP Sepharose column chromatography, Q Sepharose column chromatography, and phenyl Sepharose column chromatography
-
C-terminal quarter of the heavy chain of botulinum neurotoxin type A
P10845
cobalt affinity column chromatography, trypsinization, and QAE Sephadex A-50 anion exchange column chromatography
-
extraction of enzymatic activity of botulinum neurotoxins/A1, /A2, and /A3 from Clostridium botulinum strain Loch Maree by a panel of monoclonal anti-BoNT/A antibodies, overview
-
HisTrap column chromatography and phenyl Sepharose column chromatography
-
HisTrap column chromatography and Superdex S200 gel filtration
immobilized metal affinity chromatography or GST Sepharose affinity chromatography followed by Superdex 200 gel filtration
P10845
method is based on filtration and chromatography procedures only, which can easily be scaled up from the laboratory purification to industrial needs
-
native BoNT/A free and in complex. Recombinant His-tagged BoNT/A mutant E224A/E262A from Escherichia coli by nickel affinity chromatography, separation of the light and heavy chains
-
native BoNT/A1 and BoNT/A3, by ultrafiltration, hydrophobic interaction and anion exchange chromatography, followed by hydroxyapatite chromatography and dialysis
P10844, P10845
native BoNT/A2 toxin complex and BoNT/A2 from Clostridium botulinum A2 strain by ammonium sulfate fractionation, and by two different steps of each anion exchange and cation exchange chromatographies
-
native BONT/B from Clostridium botulinum by ion exchange chromatography
-
Ni-NTA agarose bead chromatography
Ni-NTA agarose column chromatography
Ni-NTA column chromatography
Ni-NTA column chromatography, MonoQ column chromatography, and Superdex 200 gel filtration
-
Ni2+-charged chelating Sepharose column chromatography and phenyl Sepharose column chromatography
recombinant C-terminally His-tagged wild-type and SeMet-labeled BoNT/OFD05 receptor-binding domain from Escherichia coli strain B843 (DE3) by nickel affinity chromatography, dialysis, and gel filtration
recombinant catalytically inactive BoNT/A1 mutant H223A/E224A/H227A holoprotein from Pichia pastoris by cation exchange chromatography to about 95% homogeneity. The purified ciBoNT/A1 HP is a mixed population of singlechain and nicked dichain
-
recombinant GST-tagged HC-fragments pHCAS, pHCBS, pHCCS, pHCDS, pHCES, pHCFS, and pHCGS, and the full-length BoNT/A, BoNT/B, BoNT/D, BoNT/G, and Strep-tagged pBoNTCS-Thro encoding from Escherichia coli by glutathione and streptavidin affinity chromatography, respectively
-
recombinant GST-tagged wild-type and mutant C2II components from Escherichia coli strain BL21
-
recombinant His-tagged and/or FLAG-tagged heavy chains, BoNT/G HCR, BoNT/A HCR, and BoNT/B HCR, from Escherichia coli by nickel affinity chromatography and gel filtration
recombinant His-tagged BoNT AE and EA chimeras from Escherichia coli strain BL21 by immobilized metal affinity and adsorption chromatography, followed by gel filtration, to homogeneity, near-complete conversion of the SC to a disulfide-linked DC as revealed by the appearance of the HC and LC upon SDS-PAGE in the presence of DTT
recombinant His-tagged BoNT/C1(1-430) from Escherichia coli strain B21(DE3) by nickel affinity chromatography
-
recombinant His-tagged BoNT/C1-LC from Escherichia coli strain M15[pREP4] by nickel affinity chromatography
-
recombinant His-tagged BoNT/E fragment HC1163-1256 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged truncated enzyme, residues 1-424, from Escherichia coli strain BL21(DE3) by metal ion affinity chromatography
-
recombinant His6-tagged BoNT/A heavy chain fragment from Escherichia coli by nickel affinity chromatography
P10845
recombinant His6-tagged light chains of the BoNT subtypes from Escherichia coli by nickel affinity chromatography
-
recombinantly expressed His6-tagged type B botulinum neurotoxin heavy chain transmembrane and binding domain, isolation from Escherichia coli inclusion body, purification, and refolding in a single step by Ni2+ affinity chromatography
-
scale-up, recombinant heavy chain fragment C of botulinum neurotoxin serotype E GS115
-
the light chain is purified by nickel affinity column chromatography
HisTrap column chromatography and Superdex S200 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytically inactive, mutated fragments, designated LHN, comprise the light chain and translocation domains of each neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized genes, LHN fragments, derived from BoNT serotype B, are expressed in Escherichia coli in high yield as soluble proteins
P10844, P10845
catalytically inactive, mutated fragments, designated LHN, comprise the light chain and translocation domains of each neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized genes, LHN fragments, derived from BoNT serotypes A and B, are expressed in Escherichia coli in high yield as soluble proteins
P10844, P10845
the receptor-binding domain of botulinum neurotoxin serotype B is expressed in Escherichia coli BL21(DE3) cells
BoNT/A, DNA and amino acid sequence determination, BoNT/A is produced along with six neurotoxin associated proteins, including hemagglutinin Hn-33, through polycistronic expression of a clustered group of genes to form a complex, BoNT/AC. Expresssion of His-tagged BoNT/A mutant E224A/E262A in Escherichia coli
-
bont/F, bont/A, and bont/B genes, DNA and amino acid sequence determination and analysis, comparisons, and phylogenetic analysis
bont/F, bont/A, and bont/B genes, DNA and amino acid sequence determination and analysis, phylogenetic analysis
botulinum neurotoxin complex bont genes from different strains, genotyping and phylogenetic analysis, overview
-
botulinum neurotoxin type B strains type B, Ab, and A(B) contain five different subtypes of gene bont/B. B1 subtype gene bont/B DNA sequence determination and analysis. Genomic localization of the bont/B and /A subtype genes, plasmid carriage is bont/B subtype-related. Plasmid-borne bont/B PCR-RFLP subtype genes among Clostridium botulinum strains, overview
botulinum neurotoxin type B strains type B, Ab, and A(B) contain five different subtypes of gene bont/B. B2 subtype gene bont/B DNA sequence determination and analysis. Genomic localization of the bont/B and /A subtype genes, plasmid carriage is bont/B subtype-related. Plasmid-borne bont/B PCR-RFLP subtype genes among Clostridium botulinum strains, overview
botulinum neurotoxin type B strains type B, Ab, and A(B) contain five different subtypes of gene bont/B. Bivalent subtype gene bont/B DNA sequence determination and analysis. Genomic localization of the bont/B and /A subtype genes, plasmid carriage is bont/B subtype-related. Plasmid-borne bont/B PCR-RFLP subtype genes among Clostridium botulinum strains, overview
botulinum neurotoxin type B strains type B, Ab, and A(B) contain five different subtypes of gene bont/B. Non-proteolytic subtype gene bont/B DNA sequence determination and analysis. Genomic localization of the bont/B and /A subtype genes, plasmid carriage is bont/B subtype-related. Plasmid-borne bont/B PCR-RFLP subtype genes among Clostridium botulinum strains, overview
C-terminal quarter of the heavy chain of botulinum neurotoxin type A, expression in Escherichia coli
P10845
catalytically inactive, mutated fragments, designated LHN, comprise the light chain and translocation domains of each neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized genes, LHN fragments, derived from BoNT serotype A, are expressed in Escherichia coli in high yield as soluble proteins
P10844, P10845
cell bank construction, expression of the C-terminal heavy chain fragment of botulinum neurotoxin serotype E in Pichia pastoris strain GS115, method development and evaluation using the pHILD4 Escherichia coli-Pichia pastoris shuttle plasmid, fermentation up-scaling, modeling, overview
-
cloning of the gene encoding the BoNT/A heavy chain as 1275 bp AHc fragment synthesized by PCR, and overexpression as His6-tagged protein in Escherichia coli
P10845
construction of an expression vector containing DNA encoding the enterokinase whose cleavage site positioned between LC and HC is replaced with a sequence encoding a second TEV cleavage site, His10- or GFP-tagged, expression in Escherichia coli, generation of a recombinant baculovirus containing BoNT/A LC peptide
-
DNA sequence encoding the receptor binding domain of BoNT/CD (S867-E1280) is codon-optimized for expression in Escherichia coli with a C-terminal His tag and cloned into the expression vector pJexpress411 and expressed in Escherichia coli
expressed in Escherichia coli
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli M15pREP4 cells
expressed in nonsporulating and nontoxigenic Clostridium botulinum expression host strain
-
expression in Escherichia coli strains BL21(DE3) and M15 of GST-tagged HC-fragments pHCAS, pHCBS, pHCCS, pHCDS, pHCES, pHCFS, and pHCGS, and the full-length BoNT/A, BoNT/B, BoNT/D, BoNT/G, as well as pBoNTCS-Thro encoding full-length BoNT/C fused C-terminally to a Streptag and containing an Escherichia coli protease sensitive peptide between LC and HC
-
expression of C-terminally His-tagged BoNT/C1-LC in Escherichia coli strain M15[pREP4]
-
expression of catalytically inactive BoNT/A1 mutant H223A/E224A/H227A holoprotein in Pichia pastoris
-
expression of GST-tagged wild-type and mutant C2II components in Escherichia coli strain BL21
-
expression of heavy chain fragment C of botulinum neurotoxin serotype E in Pichia pastoris
-
expression of His-tagged BoNT AE and EA chimeras in Escherichia coli strain BL21
expression of His-tagged BoNT/E fragment, composed by the 1163-1256 residues of botulinum type E neurotoxin HC gene and termed HC1163-1256, in Escherichia coli strain BL21(DE3)
-
expression of His-tagged truncated enzyme, residues 1-424, in Escherichia coli strain BL21(DE3)
-
expression of His6-tagged light chains of thr BoNT subtypes in Escherichia coli
-
expression of recombinant His-tagged and/or FLAG-tagged heavy chains, BoNT/G HCR, BoNT/A HCR, and BoNT/B HCR, in Escherichia coli strain BL21(DE3)
expression of tagged heavy chain domain, as EGFP-Hc-N/A or mCherry-Hc-N/A, in Escherichia coli strain BL21(DE3)
-
expression of the Clostridium botulinum A2 neurotoxin orfX gene cluster proteins ORFX1, ORFX3, P47, and the middle part of NTNH from Clostridium botulinum A2 strain Kyoto F, and NTNH of Clostridium botulinum A1 strain ATCC 3502 in Escherichia coli strain CA434 and in a Clostridium botulinum expression system involving type A transposon Tn916 mutant strain LNT01, expression analysis of orfX cluster genes in native A2 strain, overview
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
full length Clostridium botulinum neurotoxin type E light chain, expression in Escherichia coli
-
genes bont, 6 subtypes, DNA and amino acid sequence determination and analysis, sequence comparisons. The genes from proteolytic, group I, strains form subtypes F1 through F5, while the genes from nonproteolytic, group II, strains form subtype F6, phylogenetic analysis
genes bont, 6 subtypes, DNA and amino acid sequence determination and analysis. The genes from proteolytic, group I, strains form subtypes F1 through F5, while the genes from nonproteolytic, group II, strains form subtype F6, phylogenetic analysis
heavy and light chain DNA sequence determination, expression of GST-tagged wild-type BoNT/A light chain and of seven peptide fragments of BoNT/A light chain, Lc, L1, L2, L1-1, L1-2, L1-3, L1-4, as well as mutant L1-3 BoNT/A light chain peptide fragment in Escherichia coli strain Bl21(DE3)
-
high level overexpression by autoinduction method of botulinum neurotoxin serotype C1, comprising residues 1-430, in Escherichia coli strain BL21(DE3) as His-tagged protein
-
His6-tagged recombinant type B botulinum neurotoxin heavy chain transmembrane and binding domain, expression in Escherichia coli BL21
-
mouse microarray test to identify genes induced by injection of lysophosphatidic acid in a BoNT/C3-reversible manner
-
recombinant expression of the C-terminally His-tagged BoNT/OFD05 receptor-binding domain, wild-type and SeMet-labeled, in Escherichia coli strain B843 (DE3)
recombinant light chain type A BoNT LC expressed in Escherichia coli HB101
-
regulated expression of serotype B-LC in yeast leads to cleavage of the chimera and a conditional growth defect
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
analysis
drug development
medicine
molecular biology
-
botulinum neurotoxins BoNT/A-G are widely used as laboratory research tools
additional information
medicine
P10844, P10845
LHN/A vaccine protects mice against challenge with BoNT/A subtypes A1, A2, and A3,the LHN/B vaccine is also highly efficacious
medicine
P10844, P10845
LHN/B vaccine protects mice against challenge with BoNT/A subtypes A1, A2, and A3
analysis
-
development and evaluation of molecular detection tool for tracking and tracing Clostridium botulinum types A, B, E, F and other botulinum neurotoxin producing Clostridia using the real-time PCR-based GeneDisc cycler and BoNTs, overview. No cross reactivity with non human-toxigenic bacteria, Clostridium botulinum types C, D and G
analysis
-
the recombinant VAMP2 peptide substrate can be used as in vitro bioassay for the detection of BONT/B in food samples and provide a relevant replacement assay for the estimation of the toxin potency in contaminated therapeutic preparations
drug development
P10845
the enzyme is a target for design of specific inhibitors
drug development
P10845
because of the potential for use of the toxin in bioterrorism and the increasingly widespread application of the toxin in the medical field, there is interest in the development of small-molecule inhibitors of the metalloprotease
drug development
-
botulinum toxins are targets for rational development of preventive vaccines or inhibitors
drug development
-
ability of monoclonal antibodies F1-2 and F1-40 to provide therapeutic protection against BoNT/A intoxication in mouse intravenous and oral intoxication models, overview
drug development
-
RNA aptamers are a unique group of molecules acting as therapeutics and as an antidote against botulism
drug development
-
the BoNT/A Lc alpha-exosite is a target for inhibitor development
drug development
P10845
the botulinum toxin is a target for development of specific drugs to treat botulism
drug development
-
the toxin is a target for development of inhibitors to treat muscular paralysis, and of drugs altering BoNT/B light chain ubiquitination to overcome botulinum persistence in neuronal cells
medicine
-
BoNT/A is the best available therapeutic agent of a variety of human diseases that benefit from a finctional inhibition of cholinergic terminals
medicine
-
design of inhibitors to treat food-borne, wound and infant botulism, rare but severe diseases, moreover, the enzyme can be used as biological warfare, because of its easiness of production and very high toxicity
medicine
-
most lethal biological substance have been weaponized in highly toxic aerosol form to pose a significant dual threat to both civilian and military populations, there is an urgent need for therapeutic countermeasures against BoNTs
medicine
-
remarkably effective drug for treating a wide variety of muscle dysfunctions in humans
medicine
-
retargeting of BoNT endopeptidase into specific cells has an enormous potential of therapeutic use, not only for moderating release of hormones, peptides, and metabolites, but also disrupting cancer cell growth and functioning
medicine
-
the enzyme is a useful therapeutic agent for many human syndroms caused by hyperactivity of cholinergic nerve terminals. Human diseases treated with BoNT/A: blepharospasm, hemifacial spasm, laryngeal dysphonia, head and neck dystonias, strabismus, limb dystonias, occupational cramps, anal fissure and rectal spasms, palmar and ascellar hyperhydrosis, hypersalivation and hypersweating, migraine headache, pain, bruxism, spasticity, urinary retention and pain, essential tremors, dysphagia and achalasia esophagea. BoNT/A is extensively used as a pharmaco-cosmetic
medicine
-
botulinum neurotoxins BoNT/A-G are used as therapeutics in a variety of neuromuscular disorders of the skeletal, glandular, and smooth muscles and pain disorders
medicine
-
process development for production of a candidate vaccine antigen by recombinant expression of the C-terminal heavy chain fragment of botulinum neurotoxin serotype E Pichia pastoris strain GS115
medicine
-
BoNT/E can reduce seizure incidence in Mus musculus strain C57BL/6N, a mouse model of mesial temporal lobe epilepsy (electroencephalography analysis)
medicine
-
candidate for treatment of lower urinary tract symptoms due to benign prostatic enlargment
medicine
-
analgesic effect of BoNT/A on neuropathic pain, e.g. chronic refractory neck pain, application on human neck and shoulder muslces
medicine
-
BoNT-A can be administered subcutaneously or topically, in addition to the common application by intradermal and intramuscular injection, with a transdermal delivery peptide to reduce inflammation produced by activating nociceptors in the skin. Peptide-mediated delivery of BoNT-A is an easy and non-invasive way of administering the toxin that may prove to be useful in clinical practice, overview
medicine
-
BoNT-A treatment of bladder of human hosts, patients with neurogenic bladder dysfunction, improves bladder capacity, reflex volume, continence status, and detrusor compliance, maximum detrusor pressure iss significantly reduced, long-term effects of repeated intradetrusor BoNT-A injections on detrusor function in human hosts result in a succes rate of 74%, overview
medicine
-
BoNT/A is largely employed in human therapy because of its specific inhibition of peripheral cholinergic nerve terminals
medicine
BoNT/A is very effective in the therapy of a wide range of human syndromes characterized by hyperactivity of peripheral cholinergic nerve terminals
medicine
-
BoNT/A is widely used as a therapeutic agent and to reduce wrinkles. The toxin is used at very low doses, which have to be accurately quantified
medicine
-
BoNTs are among the most useful reagents to treat neuromuscular afflictions
medicine
-
clinical evidence on the effectiveness and reliability of minimally invasive and reversible sacral neuromodulation and botulinum toxin A treatment as well as the current significance of sacral neuromodulation and botulinum toxin A for the second-line treatment of adult syndrome of idiopathic overactive bladder, overview
medicine
-
evaluation of catalytically inactive BoNT/A1 mutant H223A/E224A/H227A holoprotein as a vaccine candidate by comparison against recombinant BoNT/A1 LC, LC-belt, LC-Hn, and Hc antigens and a LC-Hn +Hc combination in mouse potency and efficacy bioassays when challenged with BoNT/A subtypes /A1, /A2, and /A3, overview
medicine
-
Hn-33 and other neurotoxin associated proteins can potentially be employed as adjuvants for development of vaccines against botulism and can be a good surrogate for botulinum diagnostics. Medical implications of immunogenicity of different components of BoNT/A complex
medicine
P10844, P10845
LHN/A vaccine protects mice against challenge with BoNT/A subtypes A1, A2, and A3
medicine
-
localized injections of BoNT/A are widely employed in clinical neurology to treat several human diseases characterized by muscle hyperactivity
medicine
-
RNA aptamers are a unique group of molecules acting as therapeutics and as an antidote against botulism
medicine
-
a number of peptides are selected on the basis of their involvement in BoNT/A binding in vitro to snps and/or to blocking Abs, for their ability to exert an inhibitory effect on the action of the toxin in vivo
medicine
P10845, Q58GH1
subtype BoNT/A2 has greater clinical therapeutic value for treating subjects with Parkinson's disease compared to that ofsubtype BoNT/A1
additional information
-
botulinum neurotoxins are biological hazards to humans and a serious potential bioweapon threat
additional information
-
botulinum neurotoxins BoNT/A-G are the most potent of all toxins and potential bioterrorism agents, they are also used in cosmetic applications
additional information
-
the enzyme can be used as an agent in biowarfare
additional information
-
botulinum neurotoxin serotype A causes a life-threatening neuroparalytic disease known as botulism that can afflict large, unprotected populations if the toxin is employed in an act of bioterrorism
additional information
-
botulinum neurotoxin type A is the most poisonous substance known to humans and is a potential bioterrorism agent
additional information
-
development of in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors, overview
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Clostridium botulinum, Clostridium sp.
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Clostridium botulinum
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Clostridium botulinum
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Nucleotide sequence of Clostridium botulinum C1 neurotoxin
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Clostridium botulinum
Saathyamoorthy, V.; DasGupta, B.R.
Separation, purification, partial characterization and comparison of the heavy and light chains of botulinum neurotoxin types A, B, and E
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Clostridium botulinum
Thompson, D.E.; Brehm, J.K.; Oultram, J.D.; Swinfield, T.J.; Shone, C.C.; Atkinson, T.; Melling, J.; Minton, N.P.
The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene
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1990
Clostridium botulinum
Binz, T.; Kurazono, H.; Wille, M.; Frevert, J.; Wernars, K.; Niemann, H.
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265
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1990
Clostridium botulinum
Schiavo, G.; Santucci, A.; DasGupta, B.R.; Mehta, P.P.; Jontes, J.; Benfenati, F.; Wilson, M.C.; Montecucco, C.
Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds
FEBS Lett.
335
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Clostridium botulinum
Schiavo, G.; Malizio, C.; Trimble, W.S.; Polverino de Laureto, P.; Milan, G.; Sugiyama, H.; Johnson, E.A.; Montecucco, C.
Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond
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269
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1994
Clostridium botulinum, Clostridium botulinum type G
Burnett, J.C.; Schmidt, J.J.; Stafford, R.G.; Panchal, R.G.; Nguyen, T.L.; Hermone, A.R.; Vennerstrom, J.L.; McGrath, C.F.; Lane, D.J.; Sausville, E.A.; Zaharevitz, D.W.; Gussio, R.; Bavari, S.
Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity
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310
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Clostridium botulinum
Li, L.; Singh, B.R.
Role of zinc binding in type A botulinum neurotoxin light chain's toxic structure
Biochemistry
39
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2000
Clostridium botulinum
Simpson, L.L.
Identification of the characteristics that underlie botulinum toxin potency: implications for designing novel drugs
Biochimie
82
943-953
2000
Clostridium baratii, Clostridium botulinum, Clostridium butyricum
Washbourne, P.; Pellizzari, R.; Baldini, G.; Wilson, M.C.; Montecucco, C.
Botulinum neurotoxin types A and E require the SNARE motif in SNAP-25 for proteolysis
FEBS Lett.
418
1-5
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Clostridium botulinum
Adler, M.; Nicholson, J.D.; Cornille, F.; Hackley, B.E., Jr.
Efficacy of a novel metalloprotease inhibitor on botulinum neurotoxin B activity
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429
234-238
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Clostridium botulinum
Schmidt, J.J.; Stafford, R.G.; Bostian, K.A.
Type A botulinum neurotoxin proteolytic activity: development of competitive inhibitors and implications for substrate specificity at the S1' binding subsite
FEBS Lett.
435
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Clostridium botulinum
Schmidt, J.J.; Stafford, R.G.
A high-affinity competitive inhibitor of type A botulinum neurotoxin protease activity
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532
423-426
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Clostridium botulinum
Garcia, G.E.; Moorad, D.R.; Gordon, R.K.
Buforin I, a natural peptide, inhibits botulinum neurotoxin B activity in vitro
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19 Suppl 1
S19-22
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Clostridium botulinum
Anne, C.; Turcaud, S.; Quancard, J.; Teffo, F.; Meudal, H.; Fournie-Zaluski, M.C.; Roques, B.P.
Development of potent inhibitors of botulinum neurotoxin type B
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46
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2003
Clostridium botulinum
Schmidt, J.J.; Bostian, K.A.
Endoproteinase activity of type A botulinum neurotoxin: substrate requirements and activation by serum albumin
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16
19-26
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Clostridium botulinum
Antharavally, B.S.; DasGupta, B.R.
Covalent structure of botulinum neurotoxin type B; location of sulfhydryl groups and disulfide bridge and identification of C-termini of light and heavy chains
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17
417-428
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Clostridium botulinum
Sagane, Y.; Watanabe, T.; Kouguchi, H.; Sunagawa, H.; Inoue, K.; Fujinaga, Y.; Oguma, K.; Ohyama, T.
Dichain structure of botulinum neurotoxin: identification of cleavage sites in types C, D, and F neurotoxin molecules
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1999
Clostridium botulinum (P18640), Clostridium botulinum (P19321), Clostridium botulinum (P30996), Clostridium botulinum, Clostridium botulinum CB16 (P19321), Clostridium botulinum Stockholm (P18640)
Ahmed, S.A.; Byrne, M.P.; Jensen, M.; Hines, H.B.; Brueggemann, E.; Smith, L.A.
Enzymatic autocatalysis of botulinum A neurotoxin light chain
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Clostridium botulinum
Li, L.; Singh, B.R.
High-level expression, purification, and characterization of recombinant type A botulinum neurotoxin light chain
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17
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1999
Clostridium botulinum
Raffestin, S.; Marvaud, J.C.; Cerrato, R.; Dupuy, B.; Popoff, M.R.
Organization and regulation of the neurotoxin genes in Clostridium botulinum and Clostridium tetani
Anaerobe
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Clostridium botulinum
Agarwal, R.; Binz, T.; Swaminathan, S.
Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design
Biochemistry
44
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Clostridium botulinum
Schmidt, J.J.; Stafford, R.G.
Botulinum neurotoxin serotype F: identification of substrate recognition requirements and development of inhibitors with low nanomolar affinity
Biochemistry
44
4067-4073
2005
Clostridium botulinum
Agarwal, R.; Binz, T.; Swaminathan, S.
Analysis of active site residues of botulinum neurotoxin E by mutational, functional, and structural studies: Glu335Gln is an apoenzyme
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44
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Clostridium botulinum
Arndt, J.W.; Yu, W.; Bi, F.; Stevens, R.C.
Crystal structure of botulinum neurotoxin type G light chain: serotype divergence in substrate recognition
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44
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2005
Clostridium botulinum
Arndt, J.W.; Chai, Q.; Christian, T.; Stevens, R.C.
Structure of botulinum neurotoxin type D light chain at 1.65 A resolution: repercussions for VAMP-2 substrate specificity
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Clostridium botulinum
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Botulinal neurotoxins: revival of an old killer
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Clostridium botulinum
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Characterization of six type A strains of Clostridium botulinum that contain type B toxin gene sequences
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A new scaleable method for the purification of botulinum neurotoxin type E
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Clostridium botulinum
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Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates
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Clostridium botulinum
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Clostridium botulinum, Clostridium botulinum type A
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Substrate recognition strategy for botulinum neurotoxin serotype A
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Clostridium botulinum
Singh, B.R.
Botulinum neurotoxin structure, engineering, and novel cellular trafficking and targeting
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Clostridium botulinum
Segelke, B.; Knapp, M.; Kadkhodayan, S.; Balhorn, R.; Rupp, B.
Crystal structure of Clostridium botulinum neurotoxin protease in a product-bound state: Evidence for noncanonical zinc protease activity
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Clostridium botulinum
Zhou, Y.; Singh, B.R.
Cloning, high-level expression, single-step purification, and binding activity of His6-tagged recombinant type B botulinum neurotoxin heavy chain transmembrane and binding domain
Protein Expr. Purif.
34
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Clostridium botulinum
Agarwal, R.; Eswaramoorthy, S.; Kumaran, D.; Dunn, J.J.; Swaminathan, S.
Cloning, high level expression, purification, and crystallization of the full length Clostridium botulinum neurotoxin type E light chain
Protein Expr. Purif.
34
95-102
2004
Clostridium botulinum
Sharma, S.; Zhou, Y.; Singh, B.R.
Cloning, expression, and purification of C-terminal quarter of the heavy chain of botulinum neurotoxin type A
Protein Expr. Purif.
45
288-295
2006
Clostridium botulinum (P10845)
Dux, M.P.; Barent, R.; Sinha, J.; Gouthro, M.; Swanson, T.; Barthuli, A.; Inan, M.; Ross, J.T.; Smith, L.A.; Smith, T.J.; Webb, R.; Loveless, B.; Henderson, I.; Meagher, M.M.
Purification and scale-up of a recombinant heavy chain fragment C of botulinum neurotoxin serotype E in Pichia pastoris GS115
Protein Expr. Purif.
45
359-367
2006
Clostridium botulinum
Hasegawa, K.; Watanabe, T.; Sato, H.; Sagane, Y.; Mutoh, S.; Suzuki, T.; Yamano, A.; Kouguchi, H.; Takeshi, K.; Kamaguchi, A.; Fujinaga, Y.; Oguma, K.; Ohyama, T.
Characterization of toxin complex produced by a unique strain of Clostridium botulinum serotype D 4947
Protein J.
23
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2004
Clostridium botulinum
Purcell, A.L.; Hoard-Fruchey, H.M.
A capillary electrophoresis method to assay catalytic activity of botulinum neurotoxin serotypes: implications for substrate specificity
Anal. Biochem.
366
207-217
2007
Clostridium botulinum
Kaiser, E.; Haug, G.; Hliscs, M.; Aktories, K.; Barth, H.
Formation of a biologically active toxin complex of the binary Clostridium botulinum C2 toxin without cell membrane interaction
Biochemistry
45
13361-13368
2006
Clostridium botulinum
Jin, R.; Sikorra, S.; Stegmann, C.M.; Pich, A.; Binz, T.; Brunger, A.T.
Structural and biochemical studies of botulinum neurotoxin serotype C1 light chain protease: implications for dual substrate specificity
Biochemistry
46
10685-10693
2007
Clostridium botulinum, Clostridium tetani
Silvaggi, N.R.; Wilson, D.; Tzipori, S.; Allen, K.N.
Catalytic features of the botulinum neurotoxin A light chain revealed by high resolution structure of an inhibitory peptide complex
Biochemistry
47
5736-5745
2008
Clostridium botulinum (P10845), Clostridium botulinum
Kukreja, R.V.; Sharma, S.; Cai, S.; Singh, B.R.
Role of two active site Glu residues in the molecular action of botulinum neurotoxin endopeptidase
Biochim. Biophys. Acta
1774
213-222
2007
Clostridium botulinum
Capkova, K.; Yoneda, Y.; Dickerson, T.J.; Janda, K.D.
Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors
Bioorg. Med. Chem. Lett.
17
6463-6466
2007
Clostridium botulinum
Teymoortash, A.; Sommer, F.; Mandic, R.; Schulz, S.; Bette, M.; Aumueller, G.; Werner, J.A.
Intraglandular application of botulinum toxin leads to structural and functional changes in rat acinar cells
Br. J. Pharmacol.
152
161-167
2007
Clostridium botulinum
Silvaggi, N.R.; Boldt, G.E.; Hixon, M.S.; Kennedy, J.P.; Tzipori, S.; Janda, K.D.; Allen, K.N.
Structures of Clostridium botulinum neurotoxin serotype A light chain complexed with small-molecule inhibitors highlight active-site flexibility
Chem. Biol.
14
533-542
2007
Clostridium botulinum
Yerdelen, D.; Koc, F.; Sarica, Y.
Effects of botulinum toxin on strength-duration properties
Int. J. Neurosci.
117
1457-1464
2007
Clostridium botulinum
McAllister, L.A.; Hixon, M.S.; Kennedy, J.P.; Dickerson, T.J.; Janda, K.D.
Superactivation of the botulinum neurotoxin serotype A light chain metalloprotease: a new wrinkle in botulinum neurotoxin
J. Am. Chem. Soc.
128
4176-4177
2006
Clostridium botulinum
Chen, S.; Kim, J.J.; Barbieri, J.T.
Mechanism of substrate recognition by botulinum neurotoxin serotype A
J. Biol. Chem.
282
9621-9627
2007
Clostridium botulinum
Wang, J.; Meng, J.; Lawrence, G.W.; Zurawski, T.H.; Sasse, A.; Bodeker, M.O.; Gilmore, M.A.; Fernandez-Salas, E.; Francis, J.; Steward, L.E.; Aoki, K.R.; Dolly, J.O.
Novel chimeras of botulinum neurotoxin /A and /E unveil contributions from the binding, translocation and protease domains to their functional characteristics
J. Biol. Chem.
283
16993-17002
2008
Clostridium botulinum (Q00496)
Kumaran, D.; Rawat, R.; Ludivico, M.L.; Ahmed, S.A.; Swaminathan, S.
Structure and substrate based inhibitor design for clostridium botulinum neurotoxin serotype A
J. Biol. Chem.
283
18883-18891
2008
Clostridium botulinum (P10845), Clostridium botulinum
Neumeyer, T.; Schiffler, B.; Maier, E.; Lang, A.E.; Aktories, K.; Benz, R.
Clostridium botulinum C2 toxin. Identification of the binding site for chloroquine and related compounds and influence of the binding site on properties of the C2II channel
J. Biol. Chem.
283
3904-3914
2008
Clostridium botulinum
Sinha, J.; Inan, M.; Fanders, S.; Taoka, S.; Gouthro, M.; Swanson, T.; Barent, R.; Barthuli, A.; Loveless, B.M.; Smith, L.A.; Smith, T.; Henderson, I.; Ross, J.; Meagher, M.M.
Cell bank characterization and fermentation optimization for production of recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E (rBoNTE(H(c)): antigen E) by Pichia pastoris
J. Biotechnol.
127
462-474
2007
Clostridium botulinum, Clostridium botulinum NCTC 11219
Burnett, J.C.; Opsenica, D.; Sriraghavan, K.; Panchal, R.G.; Ruthel, G.; Hermone, A.R.; Nguyen, T.L.; Kenny, T.A.; Lane, D.J.; McGrath, C.F.; Schmidt, J.J.; Vennerstrom, J.L.; Gussio, R.; Solaja, B.A.; Bavari, S.
A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease
J. Med. Chem.
50
2127-2136
2007
Clostridium botulinum
Jin, R.; Rummel, A.; Binz, T.; Brunger, A.T.
Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity
Nature
444
1092-1095
2006
Clostridium botulinum
Tang, J.; Park, J.G.; Millard, C.B.; Schmidt, J.J.; Pang, Y.P.
Computer-aided lead optimization: improved small-molecule inhibitor of the zinc endopeptidase of botulinum neurotoxin serotype A
PLoS ONE
2
e761
2007
Clostridium botulinum
Fang, H.; Luo, W.; Henkel, J.; Barbieri, J.; Green, N.
A yeast assay probes the interaction between botulinum neurotoxin serotype B and its SNARE substrate
Proc. Natl. Acad. Sci. USA
103
6958-6963
2006
Clostridium botulinum
Rawat, R.; Ashraf Ahmed, S.; Swaminathan, S.
High level expression of the light chain of botulinum neurotoxin serotype C1 and an efficient HPLC assay to monitor its proteolytic activity
Protein Expr. Purif.
60
165-169
2008
Clostridium botulinum
Suzuki, T.; Kouguchi, H.; Watanabe, T.; Hasegawa, K.; Yoneyama, T.; Niwa, K.; Nishikawa, A.; Lee, J.C.; Oguma, K.; Ohyama, T.
Effect of nicking the C-terminal region of the Clostridium botulinum serotype D neurotoxin heavy chain on its toxicity and molecular properties
Protein J.
26
173-181
2007
Clostridium botulinum
Ahmed, S.A.; Olson, M.A.; Ludivico, M.L.; Gilsdorf, J.; Smith, L.A.
Identification of residues surrounding the active site of type A botulinum neurotoxin important for substrate recognition and catalytic activity
Protein J.
27
151-162
2008
Clostridium botulinum
Antonucci, F.; Bozzi, Y.; Caleo, M.
Intrahippocampal infusion of botulinum neurotoxin E (BoNT/E) reduces spontaneous recurrent seizures in a mouse model of mesial temporal lobe epilepsy
Epilepsia
50
963-966
2009
Clostridium botulinum
Oeconomou, A.; Madersbacher, H.; Kiss, G.; Berger, T.J.; Melekos, M.; Rehder, P.
Is botulinum neurotoxin type A (BoNT-A) a novel therapy for lower urinary tract symptoms due to benign prostatic enlargement? A review of the literature
Eur. Urol.
54
765-775
2008
Clostridium botulinum
Antonucci, F.; Di Garbo, A.; Novelli, E.; Manno, I.; Sartucci, F.; Bozzi, Y.; Caleo, M.
Botulinum neurotoxin E (BoNT/E) reduces CA1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy
Exp. Neurol.
210
388-401
2008
Clostridium botulinum
Uchida, H.; Matsumoto, M.; Ueda, H.
Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: ephrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia
Neurochem. Int.
54
215-221
2009
Clostridium botulinum, Clostridium botulinum C3
Nuemket, N.; Tanaka, Y.; Tsukamoto, K.; Tsuji, T.; Nakamura, K.; Kozaki, S.; Yao, M.; Tanaka, I.
Preliminary X-ray crystallographic study of the receptor-binding domain of the D/C mosaic neurotoxin from Clostridium botulinum
Acta Crystallogr. Sect. F
66
608-610
2010
Clostridium botulinum (A5JGM8), Clostridium botulinum
Tsai, C.Y.; Chiu, W.C.; Liao, Y.H.; Tsai, C.M.
Effects on craniofacial growth and development of unilateral botulinum neurotoxin injection into the masseter muscle
Am. J. Orthod. Dentofacial. Orthop.
135
142.e1-6
2009
Clostridium botulinum
Rowe, B.; Schmidt, J.J.; Smith, L.A.; Ahmed, S.A.
Rapid product analysis and increased sensitivity for quantitative determinations of botulinum neurotoxin proteolytic activity
Anal. Biochem.
396
188-193
2010
Clostridium botulinum
Ozanich, R.M.; Bruckner-Lea, C.J.; Warner, M.G.; Miller, K.; Antolick, K.C.; Marks, J.D.; Lou, J.; Grate, J.W.
Rapid multiplexed flow cytometric assay for botulinum neurotoxin detection using an automated fluidic microbead-trapping flow cell for enhanced sensitivity
Anal. Chem.
81
5783-5793
2009
Clostridium botulinum
Montal, M.
Botulinum neurotoxin: a marvel of protein design
Annu. Rev. Biochem.
79
591-617
2010
Clostridium botulinum
Roxas-Duncan, V.; Enyedy, I.; Montgomery, V.A.; Eccard, V.S.; Carrington, M.A.; Lai, H.; Gul, N.; Yang, D.C.; Smith, L.A.
Identification and biochemical characterization of small-molecule inhibitors of Clostridium botulinum neurotoxin serotype A
Antimicrob. Agents Chemother.
53
3478-3486
2009
Clostridium botulinum
Poras, H.; Ouimet, T.; Orng, S.V.; Fournie-Zaluski, M.C.; Popoff, M.R.; Roques, B.P.
Detection and quantification of botulinum neurotoxin type A by a novel rapid in vitro fluorimetric assay
Appl. Environ. Microbiol.
75
4382-4390
2009
Clostridium botulinum
De Medici, D.; Anniballi, F.; Wyatt, G.M.; Lindstroem, M.; Messelhaeusser, U.; Aldus, C.F.; Delibato, E.; Korkeala, H.; Peck, M.W.; Fenicia, L.
Multiplex PCR for detection of botulinum neurotoxin-producing clostridia in clinical, food, and environmental samples
Appl. Environ. Microbiol.
75
6457-6461
2009
Clostridium botulinum (A2I2R9), Clostridium botulinum (Q58GH1), Clostridium botulinum
Lin, G.; Tepp, W.H.; Pier, C.L.; Jacobson, M.J.; Johnson, E.A.
Expression of the Clostridium botulinum A2 neurotoxin gene cluster proteins and characterization of the A2 complex
Appl. Environ. Microbiol.
76
40-47
2010
Clostridium botulinum
Raphael, B.H.; Choudoir, M.J.; Luquez, C.; Fernandez, R.; Maslanka, S.E.
Sequence diversity of genes encoding botulinum neurotoxin type F
Appl. Environ. Microbiol.
76
4805-4812
2010
Clostridium botulinum (C5IWN7), Clostridium botulinum (D2KCK3), Clostridium botulinum (P30996), Clostridium botulinum (Q58GH1), Clostridium botulinum, Clostridium baratii (Q45851), Clostridium baratii
Muraro, L.; Tosatto, S.; Motterlini, L.; Rossetto, O.; Montecucco, C.
The N-terminal half of the receptor domain of botulinum neurotoxin A binds to microdomains of the plasma membrane
Biochem. Biophys. Res. Commun.
380
76-80
2009
Clostridium botulinum
Chang, T.W.; Blank, M.; Janardhanan, P.; Singh, B.R.; Mello, C.; Blind, M.; Cai, S.
In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin
Biochem. Biophys. Res. Commun.
396
854-860
2010
Clostridium botulinum
Henkel, J.S.; Jacobson, M.; Tepp, W.; Pier, C.; Johnson, E.A.; Barbieri, J.T.
Catalytic properties of botulinum neurotoxin subtypes A3 and A4
Biochemistry
48
2522-2528
2009
Clostridium botulinum
Fu, Z.; Chen, C.; Barbieri, J.T.; Kim, J.J.; Baldwin, M.R.
Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F
Biochemistry
48
5631-5641
2009
Clostridium botulinum (Q57236)
Kukreja, R.V.; Sharma, S.K.; Singh, B.R.
Molecular basis of activation of endopeptidase activity of botulinum neurotoxin type E
Biochemistry
49
2510-2519
2010
Clostridium botulinum
Schmitt, J.; Karalewitz, A.; Benefield, D.A.; Mushrush, D.J.; Pruitt, R.N.; Spiller, B.W.; Barbieri, J.T.; Lacy, D.B.
Structural analysis of botulinum neurotoxin type G receptor binding
Biochemistry
49
5200-5205
2010
Clostridium botulinum (Q60393)
Moghaddam, M.M.; Mousavi, L.; Shokrgozar, M.A.; Amani, J.; Nazariyan, S.; Azari, S.
Cloning and expression of a region of vesicle associated membrane protein2 (VAMP2) gene and its use as a recombinant peptide substrate for assaying clostridial neurotoxins in contaminated biologicals
Biologicals
38
113-119
2010
Clostridium botulinum
Mansour, A.A.; Mousavi, S.L.; Rasooli, I.; Nazarian, S.; Amani, J.; Farhadi, N.
Cloning, high level expression and immunogenicity of 1163-1256 residues of C-terminal heavy chain of C. botulinum neurotoxin type E
Biologicals
38
260-264
2010
Clostridium botulinum
Salzameda, N.T.; Barbieri, J.T.; Janda, K.D.
Synthetic substrate for application in both high and low throughput assays for botulinum neurotoxin B protease inhibitors
Bioorg. Med. Chem. Lett.
19
5848-5850
2009
Clostridium botulinum
Warner, M.G.; Grate, J.W.; Tyler, A.; Ozanich, R.M.; Miller, K.D.; Lou, J.; Marks, J.D.; Bruckner-Lea, C.J.
Quantum dot immunoassays in renewable surface column and 96-well plate formats for the fluorescence detection of botulinum neurotoxin using high-affinity antibodies
Biosens. Bioelectron.
25
179-184
2009
Clostridium botulinum
Pannek, J.; Goecking, K.; Bersch, U.
Long-term effects of repeated intradetrusor botulinum neurotoxin A injections on detrusor function in patients with neurogenic bladder dysfunction
BJU Int.
104
1246-1250
2009
Clostridium botulinum
Hill, K.K.; Xie, G.; Foley, B.T.; Smith, T.J.; Munk, A.C.; Bruce, D.; Smith, L.A.; Brettin, T.S.; Detter, J.C.
Recombination and insertion events involving the botulinum neurotoxin complex genes in Clostridium botulinum types A, B, E and F and Clostridium butyricum type E strains
BMC Biol.
7
66
2009
Clostridium botulinum, Clostridium butyricum
Scotcher, M.C.; Johnson, E.A.; Stanker, L.H.
Characterization of the epitope region of F1-2 and F1-5, two monoclonal antibodies to botulinum neurotoxin type A
Hybridoma
28
315-325
2009
Clostridium botulinum, Clostridium botulinum ATCC 3502
Shone, C.; Agostini, H.; Clancy, J.; Gu, M.; Yang, H.H.; Chu, Y.; Johnson, V.; Taal, M.; McGlashan, J.; Brehm, J.; Tong, X.
Bivalent recombinant vaccine for botulinum neurotoxin types A and B based on a polypeptide comprising their effector and translocation domains that is protective against the predominant A and B subtypes
Infect. Immun.
77
2795-2801
2009
Clostridium botulinum (P10844), Clostridium botulinum (P10845)
Cheng, L.W.; Stanker, L.H.; Henderson, T.D.; Lou, J.; Marks, J.D.
Antibody protection against botulinum neurotoxin intoxication in mice
Infect. Immun.
77
4305-4313
2009
Clostridium botulinum
Fach, P.; Fenicia, L.; Knutsson, R.; Wielinga, P.R.; Anniballi, F.; Delibato, E.; Auricchio, B.; Woudstra, C.; Agren, J.; Segerman, B.; de Medici, D.; van Rotterdam, B.J.
An innovative molecular detection tool for tracking and tracing Clostridium botulinum types A, B, E, F and other botulinum neurotoxin producing Clostridia based on the GeneDisc cycler
Int. J. Food Microbiol.
145
S145-151
2011
Clostridium baratii, Clostridium botulinum, Clostridium butyricum
Silhar, P.; Capkova, K.; Salzameda, N.T.; Barbieri, J.T.; Hixon, M.S.; Janda, K.D.
Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors
J. Am. Chem. Soc.
132
2868-2869
2010
Clostridium botulinum
Evans, E.R.; Skipper, P.J.; Shone, C.C.
An assay for botulinum toxin types A, B and F that requires both functional binding and catalytic activities within the neurotoxin
J. Appl. Microbiol.
107
1384-1391
2009
Clostridium botulinum
Thanongsaksrikul, J.; Srimanote, P.; Maneewatch, S.; Choowongkomon, K.; Tapchaisri, P.; Makino, S.; Kurazono, H.; Chaicumpa, W.
A V H H that neutralizes the zinc metalloproteinase activity of botulinum neurotoxin type A
J. Biol. Chem.
285
9657-9666
2010
Clostridium botulinum (P10845)
Nuss, J.E.; Ruthel, G.; Tressler, L.E.; Wanner, L.M.; Torres-Melendez, E.; Hale, M.L.; Bavari, S.
Development of cell-based assays to measure botulinum neurotoxin serotype A activity using cleavage-sensitive antibodies
J. Biomol. Screen.
15
42-51
2010
Clostridium botulinum
Shi, X.; Garcia, G.E.; Neill, R.J.; Gordon, R.K.
TCEP treatment reduces proteolytic activity of BoNT/B in human neuronal SHSY-5Y cells
J. Cell. Biochem.
107
1021-1030
2009
Clostridium botulinum
Shi, X.; Curran, J.E.; Liao, Z.; Gordon, R.K.
The biological activity of ubiquitinated BoNT/B light chain in vitro and in human SHSY-5Y neuronal cells
J. Cell. Biochem.
108
660-667
2009
Clostridium botulinum
Li, B.; Pai, R.; Cardinale, S.C.; Butler, M.M.; Peet, N.P.; Moir, D.T.; Bavari, S.; Bowlin, T.L.
Synthesis and biological evaluation of botulinum neurotoxin A protease inhibitors
J. Med. Chem.
53
2264-2276
2010
Clostridium botulinum
Kumaran, D.; Eswaramoorthy, S.; Furey, W.; Navaza, J.; Sax, M.; Swaminathan, S.
Domain organization in Clostridium botulinum neurotoxin type E is unique: its implication in faster translocation
J. Mol. Biol.
386
233-245
2009
Clostridium botulinum (Q00496), Clostridium botulinum
Dong, J.; Thompson, A.A.; Fan, Y.; Lou, J.; Conrad, F.; Ho, M.; Pires-Alves, M.; Wilson, B.A.; Stevens, R.C.; Marks, J.D.
A single-domain llama antibody potently inhibits the enzymatic activity of botulinum neurotoxin by binding to the non-catalytic alpha-exosite binding region
J. Mol. Biol.
397
1106-1118
2010
Clostridium botulinum
Caleo, M.; Antonucci, F.; Restani, L.; Mazzocchio, R.
A reappraisal of the central effects of botulinum neurotoxin type A: by what mechanism?
J. Neurochem.
109
15-24
2009
Clostridium botulinum
Rummel, A.; Haefner, K.; Mahrhold, S.; Darashchonak, N.; Holt, M.; Jahn, R.; Beermann, S.; Karnath, T.; Bigalke, H.; Binz, T.
Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation-dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor
J. Neurochem.
110
1942-1954
2009
Clostridium botulinum
Coffield, J.A.; Yan, X.
Neuritogenic actions of botulinum neurotoxin A on cultured motor neurons
J. Pharmacol. Exp. Ther.
330
352-358
2009
Clostridium botulinum
Thyagarajan, B.; Krivitskaya, N.; Potian, J.G.; Hognason, K.; Garcia, C.C.; McArdle, J.J.
Capsaicin protects mouse neuromuscular junctions from the neuroparalytic effects of botulinum neurotoxin A
J. Pharmacol. Exp. Ther.
331
361-371
2009
Clostridium botulinum
Pellett, S.; Tepp, W.H.; Toth, S.I.; Johnson, E.A.
Comparison of the primary rat spinal cord cell (RSC) assay and the mouse bioassay for botulinum neurotoxin type A potency determination
J. Pharmacol. Toxicol. Methods
61
304-310
2010
Clostridium botulinum
Sun, S.; Ossandon, M.; Kostov, Y.; Rasooly, A.
Lab-on-a-chip for botulinum neurotoxin a (BoNT-A) activity analysis
Lab Chip
9
3275-3281
2009
Clostridium botulinum
Shi, J.; Li, T.; Hou, X.; Cai, K.; Bao, S.; Liu, H.; Gao, X.; Xiao, L.; Tu, W.; Wang, Q.; Yin, J.; Wang, H.
Recombinant luminal domain of human synaptotagmin II in combination with gangliosides inhibits the toxicity of botulinum neurotoxins in mice
Microbes Infect.
12
319-323
2010
Clostridium botulinum
Agarwal, R.; Schmidt, J.J.; Stafford, R.G.; Swaminathan, S.
Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F
Nat. Struct. Mol. Biol.
16
789-794
2009
Clostridium botulinum (P30996), Clostridium botulinum
Antonucci, F.; Cerri, C.; Vetencourt, J.F.; Caleo, M.
Acute neuroprotection by the synaptic blocker botulinum neurotoxin E in a rat model of focal cerebral ischaemia
Neuroscience
169
395-401
2010
Clostridium botulinum
Stowe, G.N.; Silhar, P.; Hixon, M.S.; Silvaggi, N.R.; Allen, K.N.; Moe, S.T.; Jacobson, A.R.; Barbieri, J.T.; Janda, K.D.
Chirality holds the key for potent inhibition of the botulinum neurotoxin serotype A protease
Org. Lett.
12
756-759
2010
Clostridium botulinum
Miller, D.; Richardson, D.; Eisa, M.; Bajwa, R.J.; Jabbari, B.
Botulinum neurotoxin-A for treatment of refractory neck pain: a randomized, double-blind study
Pain Med.
10
1012-1017
2009
Clostridium botulinum
Carmichael, N.M.; Dostrovsky, J.O.; Charlton, M.P.
Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin
Pain
149
316-324
2010
Clostridium botulinum
Franciosa, G.; Maugliani, A.; Scalfaro, C.; Aureli, P.
Evidence that plasmid-borne botulinum neurotoxin type B genes are widespread among Clostridium botulinum serotype B strains
PLoS ONE
4
e4829
2009
Clostridium botulinum (A2I2U3), Clostridium botulinum (A2I2W1), Clostridium botulinum (Q08077), Clostridium botulinum (Q93G71), Clostridium botulinum
Scotcher, M.C.; McGarvey, J.A.; Johnson, E.A.; Stanker, L.H.
Epitope characterization and variable region sequence of f1-40, a high-affinity monoclonal antibody to botulinum neurotoxin type a (Hall strain)
PLoS ONE
4
e4924
2009
Clostridium botulinum
Kalb, S.R.; Lou, J.; Garcia-Rodriguez, C.; Geren, I.N.; Smith, T.J.; Moura, H.; Marks, J.D.; Smith, L.A.; Pirkle, J.L.; Barr, J.R.
Extraction and inhibition of enzymatic activity of botulinum neurotoxins/A1, /A2, and /A3 by a panel of monoclonal anti-BoNT/A antibodies
PLoS ONE
4
e5355
2009
Clostridium botulinum
Pang, Y.P.; Davis, J.; Wang, S.; Park, J.G.; Nambiar, M.P.; Schmidt, J.J.; Millard, C.B.
Small molecules showing significant protection of mice against botulinum neurotoxin serotype A
PLoS ONE
5
e10129
2010
Clostridium botulinum
Conway, J.O.; Sherwood, L.J.; Collazo, M.T.; Garza, J.A.; Hayhurst, A.
Llama single domain antibodies specific for the 7 botulinum neurotoxin serotypes as heptaplex immunoreagents
PLoS ONE
5
e8818
2010
Clostridium botulinum
Fischer, A.; Nakai, Y.; Eubanks, L.M.; Clancy, C.M.; Tepp, W.H.; Pellett, S.; Dickerson, T.J.; Johnson, E.A.; Janda, K.D.; Montal, M.
Bimodal modulation of the botulinum neurotoxin protein-conducting channel
Proc. Natl. Acad. Sci. USA
106
1330-1335
2009
Clostridium botulinum
Chen, S.; Barbieri, J.T.
Engineering botulinum neurotoxin to extend therapeutic intervention
Proc. Natl. Acad. Sci. USA
106
9180-9184
2009
Clostridium botulinum
Band, P.A.; Blais, S.; Neubert, T.A.; Cardozo, T.J.; Ichtchenko, K.
Recombinant derivatives of botulinum neurotoxin A engineered for trafficking studies and neuronal delivery
Protein Expr. Purif.
71
62-73
2010
Clostridium botulinum
Chen, R.; Shi, J.; Cai, K.; Tu, W.; Hou, X.; Liu, H.; Xiao, L.; Wang, Q.; Tang, Y.; Wang, H.
Improved soluble expression and characterization of the Hc domain of Clostridium botulinum neurotoxin serotype A in Escherichia coli by using a PCR-synthesized gene and a Trx co-expression strain
Protein Expr. Purif.
71
79-84
2010
Clostridium botulinum (P10845), Clostridium botulinum
Pires-Alves, M.; Ho, M.; Aberle, K.K.; Janda, K.D.; Wilson, B.A.
Tandem fluorescent proteins as enhanced FRET-based substrates for botulinum neurotoxin activity
Toxicon
53
392-399
2009
Clostridium botulinum
Kukreja, R.; Chang, T.W.; Cai, S.; Lindo, P.; Riding, S.; Zhou, Y.; Ravichandran, E.; Singh, B.R.
Immunological characterization of the subunits of type A botulinum neurotoxin and different components of its associated proteins
Toxicon
53
616-624
2009
Clostridium botulinum, Clostridium botulinum ATCC 3502
Baldwin, M.R.; Barbieri, J.T.
Association of botulinum neurotoxins with synaptic vesicle protein complexes
Toxicon
54
570-574
2009
Clostridium botulinum
Atassi, M.Z.
Immune recognition of BoNTs A and B: how anti-toxin antibodies that bind to the heavy chain obstruct toxin action
Toxicon
54
600-613
2009
Clostridium botulinum
Hakami, R.M.; Ruthel, G.; Stahl, A.M.; Bavari, S.
Gaining ground: assays for therapeutics against botulinum neurotoxin
Trends Microbiol.
18
164-172
2010
Clostridium baratii, Clostridium botulinum, Clostridium butyricum
Amend, B.; Castro-Diaz, D.; Chartier-Kastler, E.; De Ridder, D.; Everaert, K.; Spinelli, M.; van Keerebroeck, P.; Sievert, K.D.
[Second-line-Therapie der idiopathisch beraktiven Blase. Sakrale Neuromodulation und Botulinumtoxin A]
Urologe
49
245-252
2010
Clostridium botulinum
Webb, R.P.; Smith, T.J.; Wright, P.; Brown, J.; Smith, L.A.
Production of catalytically inactive BoNT/A1 holoprotein and comparison with BoNT/A1 subunit vaccines against toxin subtypes A1, A2, and A3
Vaccine
27
4490-4497
2009
Clostridium botulinum
Niwa, K.; Yoneyama, T.; Ito, H.; Taira, M.; Chikai, T.; Kouguchi, H.; Suzuki, T.; Hasegawa, K.; Miyata, K.; Inui, K.; Ikeda, T.; Watanabe, T.; Ohyama, T.
Sialic acid-dependent binding and transcytosis of serotype D botulinum neurotoxin and toxin complex in rat intestinal epithelial cells
Vet. Microbiol.
141
312-320
2010
Clostridium botulinum
Wang, H.H.; Riding, S.; Lindo, P.; Singh, B.R.
Endopeptidase activities of botulinum neurotoxin type B complex, holotoxin, and light chain
Appl. Environ. Microbiol.
76
6658-6663
2010
Clostridium botulinum
Kalb, S.R.; Baudys, J.; Egan, C.; Smith, T.J.; Smith, L.A.; Pirkle, J.L.; Barr, J.R.
Different substrate recognition requirements for cleavage of synaptobrevin-2 by Clostridium baratii and Clostridium botulinum type F neurotoxins
Appl. Environ. Microbiol.
77
1301-1308
2011
Clostridium baratii, Clostridium botulinum
Jacobson, M.J.; Lin, G.; Tepp, W.; Dupuy, J.; Stenmark, P.; Stevens, R.C.; Johnson, E.A.
Purification, modeling, and analysis of botulinum neurotoxin subtype A5 (BoNT/A5) from Clostridium botulinum strain A661222
Appl. Environ. Microbiol.
77
4217-4222
2011
Clostridium botulinum (C7BEA8), Clostridium botulinum
Zhang, Y.; Buchko, G.W.; Qin, L.; Robinson, H.; Varnum, S.M.
Crystal structure of the receptor binding domain of the botulinum C-D mosaic neurotoxin reveals potential roles of lysines 1118 and 1136 in membrane interactions
Biochem. Biophys. Res. Commun.
404
407-412
2011
Clostridium botulinum (Q5DW55), Clostridium botulinum
Pellett, S.; Tepp, W.H.; Stanker, L.H.; Band, P.A.; Johnson, E.A.; Ichtchenko, K.
Neuronal targeting, internalization, and biological activity of a recombinant atoxic derivative of botulinum neurotoxin A
Biochem. Biophys. Res. Commun.
405
673-677
2011
Clostridium botulinum
Chen, S.; Wan, H.Y.
Molecular mechanisms of substrate recognition and specificity of botulinum neurotoxin serotype F
Biochem. J.
433
277-284
2011
Clostridium botulinum
Capkova, K.; Hixon, M.; Pellett, S.; Barbieri, J.; Johnson, E.; Janda, K.
Benzylidene cyclopentenediones: First irreversible inhibitors against botulinum neurotoxin As zinc endopeptidase
Bioorg. Med. Chem. Lett.
20
206-208
2010
Clostridium botulinum
Li, B.; Cardinale, S.C.; Butler, M.M.; Pai, R.; Nuss, J.E.; Peet, N.P.; Bavari, S.; Bowlin, T.L.
Time-dependent botulinum neurotoxin serotype A metalloprotease inhibitors
Bioorg. Med. Chem.
19
7338-7348
2011
Clostridium botulinum
Kumar, G.; Agarwal, R.; Swaminathan, S.
Discovery of a fluorene class of compounds as inhibitors of botulinum neurotoxin serotype E by virtual screening
Chem. Commun. (Camb. )
48
2412-2414
2012
Clostridium botulinum
Hale, M.; Oyler, G.; Swaminathan, S.; Ahmed, S.A.
Basic tetrapeptides as potent intracellular inhibitors of type A botulinum neurotoxin protease activity
J. Biol. Chem.
286
1802-1811
2011
Clostridium botulinum
Benson, M.A.; Fu, Z.; Kim, J.J.; Baldwin, M.R.
Unique ganglioside recognition strategies for clostridial neurotoxins
J. Biol. Chem.
286
34015-34022
2011
Clostridium botulinum (Q57236)
Gul, N.; Smith, L.; Ahmed, S.
Light chain separated from the rest of the type a botulinum neurotoxin molecule is the most catalytically active form
PLoS ONE
5
e12872
2010
Clostridium botulinum
Atassi, M.Z.; Dolimbek, B.Z.; Steward, L.E.; Aoki, K.R.
Inhibition of botulinum neurotoxin a toxic action in vivo by synthetic synaptosome- and blocking antibody-binding regions
Protein J.
29
320-327
2010
Clostridium botulinum
Bagramyan, K.; Kaplan, B.; Cheng, L.; Strotmeier, J.; Rummel, A.; Kalkum, M.
Substrates and controls for the quantitative detection of active botulinum neurotoxin in protease-containing samples
Anal. Chem.
85
5569-5576
2013
Clostridium botulinum
Tepp, W.; Lin, G.; Johnson, E.
Purification and characterization of a novel subtype A3 botulinum neurotoxin
Appl. Environ. Microbiol.
78
3108-3113
2012
Clostridium botulinum (B1L2G4), Clostridium botulinum, Clostridium botulinum A3 (B1L2G4)
Dunning, F.; Ruge, D.; Piazza, T.; Stanker, L.; Zeytin, F.; Tucker, W.
Detection of botulinum neurotoxin serotype A, B, and F proteolytic activity in complex matrices with picomolar to femtomolar sensitivity
Appl. Environ. Microbiol.
78
7687-7697
2012
Clostridium botulinum
Bradshaw, M.; Tepp, W.; Whitemarsh, R.; Pellett, S.; Johnson, E.
Holotoxin activity of botulinum neurotoxin subtype A4 originating from a nontoxigenic Clostridium botulinum expression system
Appl. Environ. Microbiol.
80
7415-7422
2014
Clostridium botulinum, Clostridium botulinum 657Ba
Inui, K.; Sagane, Y.; Miyata, K.; Miyashita, S.; Suzuki, T.; Shikamori, Y.; Ohyama, T.; Niwa, K.; Watanabe, T.
Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein
Biochem. Biophys. Res. Commun.
419
500-504
2012
Clostridium botulinum (A5HZZ9), Clostridium botulinum (A7GBG3), Clostridium botulinum (B1INP5), Clostridium botulinum (P18640)
Lee, K.; Lam, K.; Kruel, A.; Perry, K.; Rummel, A.; Jin, R.
High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex
Biochem. Biophys. Res. Commun.
446
568-573
2014
Clostridium botulinum, Clostridium botulinum Okra
Itakura, M.; Kohda, T.; Kubo, T.; Semi, Y.; Azuma, Y.; Nakajima, H.; Kozaki, S.; Takeuchi, T.
Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinsons disease model
Biochem. Biophys. Res. Commun.
447
311-314
2014
Clostridium botulinum (P10845), Clostridium botulinum (Q58GH1), Clostridium botulinum Chiba-H (Q58GH1), Clostridium botulinum 62A (P10845)
Sun, S.; Tepp, W.; Johnson, E.; Chapman, E.
Botulinum neurotoxins B and E translocate at different rates and exhibit divergent responses to GT1b and low pH
Biochemistry
51
5655-5662
2012
Clostridium botulinum (P10844), Clostridium botulinum (Q00496)
Wang, D.; Krilich, J.; Pellett, S.; Baudys, J.; Tepp, W.; Barr, J.; Johnson, E.; Kalb, S.
Comparison of the catalytic properties of the botulinum neurotoxin subtypes A1 and A5
Biochim. Biophys. Acta
1834
2722-2728
2013
Clostridium botulinum (C7BEA8), Clostridium botulinum (Q7B8V4), Clostridium botulinum, Clostridium botulinum Hall A hyper (Q7B8V4), Clostridium botulinum A661222 (C7BEA8)
Kumar, R.; Kukreja, R.; Cai, S.; Singh, B.
Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin
Biochim. Biophys. Acta
1844
1145-1152
2014
Clostridium botulinum (P10844), Clostridium botulinum (Q00496), Clostridium botulinum (Q7B8V4)
Chellappan, G.; Kumar, R.; Santos, E.; Goyal, D.; Cai, S.; Singh, B.
Structural and functional analysis of botulinum neurotoxin subunits for pH-dependent membrane channel formation and translocation
Biochim. Biophys. Acta
1854
1510-1516
2015
Clostridium botulinum (Q7B8V4), Clostridium botulinum Hall (Q7B8V4)
Kumar, R.; Cai, S.; Ojadi, E.; Singh, B.
Resolution of sub-nanosecond motions in botulinum neurotoxin endopeptidase: An evidence of internal flexibility
Biochim. Biophys. Acta
1854
321-326
2015
Clostridium botulinum (Q7B8V4)
Zhang, Y.; Gardberg, A.; Edwards, T.; Sankaran, B.; Robinson, H.; Varnum, S.; Buchko, G.
Structural insights into the functional role of the Hcn sub-domain of the receptor-binding domain of the botulinum neurotoxin mosaic serotype C/D
Biochimie
95
1379-1385
2013
Clostridium botulinum (Q5DW55), Clostridium botulinum
Seki, H.; Pellett, S.; Silhar, P.; Stowe, G.; Blanco, B.; Lardy, M.; Johnson, E.; Janda, K.
Synthesis/biological evaluation of hydroxamic acids and their prodrugs as inhibitors for botulinum neurotoxin A light chain
Bioorg. Med. Chem.
22
1208-1217
2014
Clostridium botulinum (A5HZZ9), Clostridium botulinum Hall (A5HZZ9)
Bremer, P.; Hixon, M.; Janda, K.
Benzoquinones as inhibitors of botulinum neurotoxin serotype A
Bioorg. Med. Chem.
22
3971-3981
2014
Clostridium botulinum (A5HZZ9)
Seki, H.; Xue, S.; Hixon, M.; Pellett, S.; Reme, M.; Johnson, E.; Janda, K.
Toward the discovery of dual inhibitors for botulinum neurotoxin A: Concomitant targeting of endocytosis and light chain protease activity
Chem. Commun. (Camb. )
51
6226-6229
2015
Clostridium botulinum (A5HZZ9)
Pirazzini, M.; Henke, T.; Rossetto, O.; Mahrhold, S.; Krez, N.; Rummel, A.; Montecucco, C.; Binz, T.
Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain
FEBS Lett.
587
3831-3836
2013
Clostridium botulinum (P10844), Clostridium botulinum Okra (P10844)
Vijayalakshmi Ayyar, B.; Roger Aoki, K.; Zouhair Atassi, M.
The C-terminal heavy-chain domain of botulinum neurotoxin A is not the only site that binds neurons, as the N-terminal heavy-chain domain also plays a very active role in toxin-cell binding and interactions
Infect. Immun.
83
1465-1476
2015
Clostridium botulinum, Clostridium botulinum Okra
Mizanur, R.; Frasca, V.; Swaminathan, S.; Bavari, S.; Webb, R.; Smith, L.; Ahmed, S.
The C terminus of the catalytic domain of type A botulinum neurotoxin may facilitate product release from the active site
J. Biol. Chem.
288
24223-24233
2013
Clostridium botulinum
Guo, J.; Chen, S.
Unique substrate recognition mechanism of the botulinum neurotoxin D light chain
J. Biol. Chem.
288
27881-27887
2013
Clostridium botulinum (P19321)
Kumar, R.; Kukreja, R.; Li, L.; Zhmurov, A.; Kononova, O.; Cai, S.; Ahmed, S.; Barsegov, V.; Singh, B.
Botulinum neurotoxin: Unique folding of enzyme domain of the most-poisonous poison
J. Biomol. Struct. Dyn.
32
804-815
2014
Clostridium botulinum (P10845)
Dadgar, S.; Ramjan, Z.; Floriano, W.
Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype A
J. Med. Chem.
56
2791-2803
2013
Clostridium botulinum (P10845)
Opsenica, I.; Tot, M.; Gomba, L.; Nuss, J.; Sciotti, R.; Bavari, S.; Burnett, J.; Solaja, B.
4-amino-7-chloroquinolines: Probing ligand efficiency provides botulinum neurotoxin serotype a light chain inhibitors with significant antiprotozoal activity
J. Med. Chem.
56
5860-5871
2013
Clostridium botulinum (P10845)
Matsui, T.; Gu, S.; Lam, K.; Carter, L.; Rummel, A.; Mathews, I.; Jin, R.
Structural basis of the pH-dependent assembly of a botulinum neurotoxin complex
J. Mol. Biol.
426
3773-3782
2014
Clostridium botulinum (P10845)
Berntsson, R.; Peng, L.; Dong, M.; Stenmark, P.
Structure of dual receptor binding to botulinum neurotoxin B
Nat. Commun.
4
2058
2013
Clostridium botulinum (Q33CP3)
Benoit, R.; Frey, D.; Hilbert, M.; Kevenaar, J.; Wieser, M.; Stirnimann, C.; McMillan, D.; Ceska, T.; Lebon, F.; Jaussi, R.; Steinmetz, M.; Schertler, G.; Hoogenraad, C.; Capitani, G.; Kammerer, R.
Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A
Nature
505
108-111
2014
Clostridium botulinum (P10845)
Ben David, A.; Torgeman, A.; Barnea, A.; Zichel, R.
Expression, purification and characterization of the receptor-binding domain of botulinum neurotoxin serotype B as a vaccine candidate
Protein Expr. Purif.
110
122-129
2015
Clostridium botulinum (P10844), Clostridium botulinum B (P10844)
Guo, J.; Chen, S.
Expression and biochemical characterization of light chains of Botulinum neurotoxin subtypes F5 and F7
Protein Expr. Purif.
111
87-90
2015
Clostridium botulinum, Clostridium botulinum (D2KHS9)
Singh, A.; Sachdeva, A.; Degrasse, J.; Croley, T.; Stanker, L.; Hodge, D.; Sharma, S.
Purification and characterization of neurotoxin complex from a dual toxin gene containing Clostridium botulinum strain PS-5
Protein J.
32
288-296
2013
Clostridium botulinum (P10844), Clostridium botulinum (P10845), Clostridium botulinum PS-5 (P10844), Clostridium botulinum PS-5 (P10845)
Guo, J.; Wang, J.; Chan, E.; Chen, S.
Exploration of endogenous substrate cleavage by various forms of botulinum neurotoxins
Toxicon
100
42-45
2015
Clostridium botulinum
Pellett, S.; Tepp, W.; Scherf, J.; Pier, C.; Johnson, E.
Activity of botulinum neurotoxin type D (strain 1873) in human neurons
Toxicon
101
63-69
2015
Clostridium botulinum, Clostridium botulinum 1873
Montgomery, V.; Ahmed, S.; Olson, M.; Mizanur, R.; Stafford, R.; Roxas-Duncan, V.; Smith, L.
Ex vivo inhibition of Clostridium botulinum neurotoxin types B, C, E, and F by small molecular weight inhibitors
Toxicon
98
12-19
2015
Clostridium botulinum
Kalb, S.R.; Baudys, J.; Raphael, B.H.; Dykes, J.K.; Luquez, C.; Maslanka, S.E.; Barr, J.R.
Functional characterization of botulinum neurotoxin serotype H as a hybrid of known serotypes F and A (BoNT F/A)
Anal. Chem.
87
3911-3917
2015
Clostridium botulinum, Clostridium botulinum IBCA10-7060
Minnow, Y.V.; Goldberg, R.; Tummalapalli, S.R.; Rotella, D.P.; Goodey, N.M.
Mechanism of inhibition of botulinum neurotoxin type A light chain by two quinolinol compounds
Arch. Biochem. Biophys.
618
15-22
2017
Clostridium botulinum
Kumar, G.; Agarwal, R.; Swaminathan, S.
Small molecule non-peptide inhibitors of botulinum neurotoxin serotype E Structure-activity relationship and a pharmacophore model
Bioorg. Med. Chem.
24
3978-3985
2016
Clostridium botulinum
Harrell, W.A.; Vieira, R.C.; Ensel, S.M.; Montgomery, V.; Guernieri, R.; Eccard, V.S.; Campbell, Y.; Roxas-Duncan, V.; Cardellina, J.H.; Webb, R.P.; Smith, L.A.
A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A
Bioorg. Med. Chem. Lett.
27
675-678
2017
Clostridium botulinum
Kerscher, M.; Wanitphakdeedecha, R.; Trindade de Almeida, A.; Maas, C.; Frevert, J.
IncobotulinumtoxinA A highly purified and precisely manufactured botulinum neurotoxin type A
J. Drugs Dermatol.
18
52-57
2019
Clostridium botulinum, Clostridium botulinum Hall
Sikorra, S.; Litschko, C.; Mueller, C.; Thiel, N.; Galli, T.; Eichner, T.; Binz, T.
Identification and characterization of botulinum neurotoxin A substrate binding pockets and their re-engineering for human SNAP-23
J. Mol. Biol.
428
372-384
2016
Clostridium botulinum
Davies, J.R.; Rees, J.; Liu, S.M.; Acharya, K.R.
High resolution crystal structures of Clostridium botulinum neurotoxin A3 and A4 binding domains
J. Struct. Biol.
202
113-117
2018
Clostridium botulinum (Q3LRX8), Clostridium botulinum (Q3LRX9), Clostridium botulinum
Kohda, T.; Nakamura, K.; Hosomi, K.; Torii, Y.; Kozaki, S.; Mukamoto, M.
Characterization of the functional activity of botulinum neurotoxin subtype B6
Microbiol. Immunol.
61
482-489
2017
Clostridium botulinum, Clostridium botulinum Osaka05
Moritz, M.S.; Tepp, W.H.; Bradshaw, M.; Johnson, E.A.; Pellett, S.
Isolation and characterization of the novel botulinum neurotoxin A subtype 6
mSphere
3
e00466-18
2018
Clostridium botulinum, Clostridium botulinum CDC41370
Zhang, S.; Masuyer, G.; Zhang, J.; Shen, Y.; Lundin, D.; Henriksson, L.; Miyashita, S.I.; Martinez-Carranza, M.; Dong, M.; Stenmark, P.
Identification and characterization of a novel botulinum neurotoxin
Nat. Commun.
8
14130
2017
Clostridium botulinum (P0DPK1)
Tao, L.; Peng, L.; Berntsson, R.P.; Liu, S.M.; Park, S.; Yu, F.; Boone, C.; Palan, S.; Beard, M.; Chabrier, P.E.; Stenmark, P.; Krupp, J.; Dong, M.
Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors
Nat. Commun.
8
53
2017
Clostridium botulinum
Liu, Q.; Sinnen, B.L.; Boxer, E.E.; Schneider, M.W.; Grybko, M.J.; Buchta, W.C.; Gibson, E.S.; Wysoczynski, C.L.; Ford, C.P.; Gottschalk, A.; Aoto, J.; Tucker, C.L.; Kennedy, M.J.
A photoactivatable botulinum neurotoxin for inducible control of neurotransmission
Neuron
101
863-875.e6
2019
Clostridium botulinum (P10844)
Lam, K.H.; Sikorra, S.; Weisemann, J.; Maatsch, H.; Perry, K.; Rummel, A.; Binz, T.; Jin, R.
Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA
Pathog. Dis.
76
fty044
2018
Clostridium botulinum, Clostridium botulinum BCA10-7060
Kull, S.; Schulz, K.M.; Weisemann, J.; Kirchner, S.; Schreiber, T.; Bollenbach, A.; Dabrowski, P.W.; Nitsche, A.; Kalb, S.R.; Dorner, M.B.; Barr, J.R.; Rummel, A.; Dorner, B.G.
Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype
PLoS ONE
10
e0116381
2015
Clostridium botulinum, Clostridium botulinum Chemnitz
Chauhan, R.; Chauhan, V.; Rao, M.K.; Chaudhary, D.; Bhagyawant, S.; Dhaked, R.K.
High level expression and immunochemical characterization of botulinum neurotoxin type F light chain
Protein Expr. Purif.
146
51-60
2018
Clostridium botulinum
Dhaliwal, H.K.; Thiruvanakarasu, N.; Kumar, R.; Patel, K.; Ambrin, G.; Cai, S.; Singh, B.R.
High yield preparation of functionally active catalytic-translocation domain module of botulinum neurotoxin type A that exhibits uniquely different enzyme kinetics
Protein J.
36
489-501
2017
Clostridium botulinum
Elliott, M.; Favre-Guilmard, C.; Liu, S.M.; Maignel, J.; Masuyer, G.; Beard, M.; Boone, C.; Carre, D.; Kalinichev, M.; Lezmi, S.; Mir, I.; Nicoleau, C.; Palan, S.; Perier, C.; Raban, E.; Zhang, S.; Dong, M.; Stenmark, P.; Krupp, J.
Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models
Sci. Adv.
5
eaau7196
2019
Clostridium botulinum
Masuyer, G.; Davies, J.R.; Moore, K.; Chaddock, J.A.; Ravi Acharya, K.
Structural analysis of Clostridium botulinum neurotoxin type D as a platform for the development of targeted secretion inhibitors
Sci. Rep.
5
13397
2015
Clostridium botulinum (P19321), Clostridium botulinum
Guo, J.; Chan, E.W.; Chen, S.
Mechanism of substrate recognition by the novel botulinum neurotoxin subtype F5
Sci. Rep.
6
19875
2016
Clostridium botulinum
Masuyer, G.; Zhang, S.; Barkho, S.; Shen, Y.; Henriksson, L.; Ko?enina, S.; Dong, M.; Stenmark, P.
Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity
Sci. Rep.
8
4518
2018
Clostridium botulinum (P0DPK1)
Feltrup, T.M.; Patel, K.; Kumar, R.; Cai, S.; Singh, B.R.
A novel role of C-terminus in introducing a functionally flexible structure critical for the biological activity of botulinum neurotoxin
Sci. Rep.
8
8884
2018
Clostridium botulinum
Ambrin, G.; Kumar, R.; Singh, B.R.
Differential endopeptidase activity of different forms of type A botulinum neurotoxin A unique relationship between the size of the substrate and activity of the enzyme
Toxicon
144
34-41
2018
Clostridium botulinum
Hackett, G.; Moore, K.; Burgin, D.; Hornby, F.; Gray, B.; Elliott, M.; Mir, I.; Beard, M.
Purification and characterization of recombinant botulinum neurotoxin serotype FA, also known as serotype H
Toxins
10
E195
2018
Clostridium botulinum, Clostridium botulinum IBCA 10-7060
Sikorra, S.; Skiba, M.; Dorner, M.B.; Weisemann, J.; Weil, M.; Valdezate, S.; Davletov, B.; Rummel, A.; Dorner, B.G.; Binz, T.
Botulinum neurotoxin F subtypes cleaving the VAMP-2 Q58-K59 peptide bond exhibit unique catalytic properties and substrate specificities
Toxins
10
E311
2018
Clostridium botulinum (A0A1P8YWK9), Clostridium botulinum (A7GBG3), Clostridium botulinum (D2KHS4), Clostridium baratii (A0A1P8YWP1), Clostridium baratii CNM1212/11 (A0A1P8YWP1), Clostridium botulinum NCTC 10281 (A7GBG3), Clostridium botulinum H078-01 (A0A1P8YWK9), Clostridium botulinum H078-01 (D2KHS4)
Joussain, C.; Le Coz, O.; Pichugin, A.; Marconi, P.; Lim, F.; Sicurella, M.; Salonia, A.; Montorsi, F.; Wandosell, F.; Foster, K.; Giuliano, F.; Epstein, A.L.; Aranda Munoz, A.
Botulinum neurotoxin light chains expressed by defective herpes simplex virus type-1 vectors cleave SNARE proteins and inhibit CGRP release in rat sensory neurons
Toxins
11
E123
2019
Clostridium botulinum (P0DPI1), Clostridium botulinum (P19321), Clostridium botulinum (P30996), Clostridium botulinum (Q00496), Clostridium phage c-st (P18640), Clostridium botulinum ATCC 3502 (P0DPI1)
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