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Information on EC 3.4.24.83 - anthrax lethal factor endopeptidase and Organism(s) Bacillus anthracis and UniProt Accession P15917
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3.4.24.83 anthrax lethal factor endopeptidaseSpecify your search results
Word Map
- 3.4.24.83
-
edema
- spore
-
intoxication
- endosomal
-
exotoxin
- metalloprotease
-
inhalation
- inflammasome
-
endocytosis
-
toxin-induced
-
anti-pa
-
heptameric
- caspase-1
- sterne
- furin
- mapkks
-
lt-induced
-
tripartite
- diphtheria
-
toxin-mediated
-
spore-forming
-
pyroptosis
- toxemia
-
ring-shaped
-
receptor-bound
-
toxin-neutralizing
-
zinc-dependent
- molecular biology
-
cytolysis
-
pa-binding
- medicine
- mkk
-
bioterrorism
- diagnostics
-
toxin-sensitive
- synthesis
-
postexposure
-
cell-binding
The taxonomic range for the selected organisms is: Bacillus anthracis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Preferred amino acids around the cleavage site can be denoted BBBBxHx-/-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases
Synonyms
lethal factor, anthrax lethal toxin, anthrax lethal factor, bacillus anthracis lethal toxin, anthrax toxin lethal factor, anthrax lf, anthrax lethal factor protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
anthrax lethal toxin
anthrax lethal factor
anthrax lethal toxin
lethal factor
lethal factor of anthrax toxin
the C-terminal region carries out the metalloprotease activity, while the N-terminal domain (residues 1-288) is responsible for protective antigen binding
lethal toxin
LeTx
LF
-
-
-
-
anthrax lethal toxin
protective antigen plus lethal factor makes lethal toxin
anthrax lethal factor
-
-
anthrax lethal factor
-
anthrax lethal factor along with its receptor-binding partner protective antigen forms anthrax lethal toxin
anthrax lethal factor
-
anthrax lethal factor is part of the bipartite anthrax lethal toxin
anthrax lethal toxin
-
-
anthrax lethal toxin
-
the pathological actions of anthrax toxin require the activities of its edema factor and lethal factor enzyme components which gain intracellular access via its receptor-binding component, protective antigen
lethal factor
-
lethal factor combines with protective antigen to form antrax lethal toxin
lethal factor
-
lethal toxin is secreted by Bacillus anthracis as a bipartite toxin consisting of protective antigen (PA) and lethal factor (LF)
lethal toxin
-
-
-
-
LeTx
-
-
LeTx
-
lethal toxin is composed of lethal factor and the protective antigen
LeTx
-
protective antigen from Bacillus anthracis binds to cellular receptors, combines with lethal factor forming lethal toxin LeTx, and facilitates the translocation of lethal factor into the cytosol
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Preferred amino acids around the cleavage site can be denoted BBBBxHx-/-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases
Preferred amino acids around the cleavage site can be denoted BBBBxHx-/-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases
mechanism
-
Preferred amino acids around the cleavage site can be denoted BBBBxHx-/-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases
From the bacterium Bacilus anthracis that causes anthrax. One of three proteins that are collectively termed anthrax toxin. Cleaves several MAP kinase kinases near their N-termini, preventing them from phosphorylating the downstream mitogen-activated protein kinases
-
Preferred amino acids around the cleavage site can be denoted BBBBxHx-/-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases
pre-steady-state kinetics of anthrax lethal factor proteolysis follows a four-step mechanism as follows: initial substrate binding, rearrangement of the enzyme-substrate complex, a rate-limiting cleavage step, and product release
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
477950-41-7
-
9001-92-7
-
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
(7-methoxycoumarin-4-yl)acetyl-AKVYPYPME-(2,4-dinitrophenyldiaminopropionic acid) + H2O
(7-methoxycoumarin-4-yl)acetyl-AKVYP + YPME-(2,4-dinitrophenyldiaminopropionic acid)
-
-
-
?
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide + H2O
?
-
-
-
?
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin + H2O
?
-
-
-
?
NACHT leucine-rich repeat and pyrin domain-containing protein 1B + H2O
?
-
-
-
?
NOD-like receptor protein-1 + H2O
?
lethal factor cleaves rat NOD-like receptor protein Nlrp1. Cleavage is required for toxin-induced inflammasome activation, interleukin IL-1beta release, and macrophage pyroptosis
-
-
?
83 kDa full-length protective antigen + H2O
20 kDa N-terminal fragment of protective antigen + 63 kDa N-terminal fragment of protective antigen
-
-
-
?
AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R-4-nitroanilide + H2O
AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R + 4-nitroaniline
-
-
-
-
?
AcM-L-A-R-R-R-P-V-L-P-4-nitroanilide + H2O
AcM-L-A-R-R-R-P-V-L-P + 4-nitroaniline
-
-
-
-
?
AcR-R-R-R-V-L-R-4-methylcoumarin-7-amide + H2O
AcR-R-R-R-V-L-R + 7-amino-4-methylcoumarin
-
-
-
-
?
AcR-R-R-R-V-L-R-4-nitroanilide + H2O
AcR-R-R-R-V-L-R + 4-nitroaniline
-
-
-
-
?
dansyl-RDIRRITLFSLH
?
-
i.e. S20D, substrate isolated from phage library
-
-
?
Dsor1 kinase + H2O
?
-
Dsor1 is a Drosophila mitogen-activated protein kinase kinase
-
-
?
fluorescein-QRRKKVYPYPME + H2O
fluorescein-QRRKKVYP + YPME
-
i.e. LF15, peptide substrate isolated from second-iteration substrate phage library
-
-
?
Hep kinase + H2O
?
-
Hep (Hemipterous) is a Drosophila mitogen-activated protein kinase kinase
incubation of Hep with anthrax lethal factor generates a product of about 44 kDa
-
?
Lic kinase + H2O
?
-
Lic (Licorne) is a Drosophila mitogen-activated protein kinase kinase
-
-
?
MEK2 + H2O
?
-
mitogen-activated protein kinase kinase, cleavage between residues 10-11
-
-
?
MKK3b + H2O
?
-
mitogen-activated protein kinase kinase, cleavage between residues 26-27
-
-
?
MKK4 + H2O
?
-
mitogen-activated protein kinase kinase, cleavage between residues 45-46 and 58-59
-
-
?
MKK6b + H2O
?
-
mitogen-activated protein kinase kinase, cleavage between residues 14-15
-
-
?
MKK7beta + H2O
?
-
mitogen-activated protein kinase kinase, cleavage between residues 44-45 and 76-77
-
-
?
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide + H2O
?
commercial substrate S-pNA
-
-
?
MEK1 + H2O
?
-
mitogen-activated protein kinase kinase, cleavage between residues 8-9
-
-
?
mitogen-activated protein kinase + H2O
?
-
-
-
-
?
mitogen-activated protein kinase + H2O
?
-
cleavage within N-terminus of MAPKKs
-
-
?
mitogen-activated protein kinase + H2O
?
-
substrate: MAPKK4, MAPKK6, MAPKK7, no substrate: MAPKK5
-
-
?
mitogen-activated protein kinase + H2O
?
-
substrate: MAPKK3, i.e. MKK3
-
-
?
mitogen-activated protein kinase + H2O
?
-
substrates: MAPKK1, MAPKK2
-
-
?
mitogen-activated protein kinase + H2O
?
-
inactivation of substrate
-
-
?
mitogen-activated protein kinase kinase + H2O
?
-
-
-
-
?
mitogen-activated protein kinase kinase + H2O
?
-
anthrax lethal toxin cleaves mitogen-activated protein kinase kinase/MEK/MAPKK 1-4 and 6, but not mitogen-activated protein kinase kinase 5 and 7 in murine neutrophils
-
-
?
mitogen-activated protein kinase kinase 1 + H2O
?
-
specifically cleaves the aminoterminal 7 amino acids of mitogen-activated protein kinase kinases
-
-
?
mitogen-activated protein kinase kinase 1 + H2O
?
-
all but one of the mitogen-activated protein kinase kinases (MEK) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates
-
-
?
mitogen-activated protein kinase kinase 2 + H2O
?
-
specifically cleaves the aminoterminal 7 amino acids of mitogen-activated protein kinase kinases
-
-
?
mitogen-activated protein kinase kinase 2 + H2O
?
-
all but one of the mitogen-activated protein kinase kinases (MEK) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates
-
-
?
mitogen-activated protein kinase kinase 3 + H2O
?
-
specifically cleaves the aminoterminal 7 amino acids of mitogen-activated protein kinase kinases
-
-
?
mitogen-activated protein kinase kinase 3 + H2O
?
-
all but one of the mitogen-activated protein kinase kinases (MEK) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates
-
-
?
mitogen-activated protein kinase kinase 4 + H2O
?
-
specifically cleaves the aminoterminal 7 amino acids of mitogen-activated protein kinase kinases
-
-
?
mitogen-activated protein kinase kinase 4 + H2O
?
-
all but one of the mitogen-activated protein kinase kinases (MEK) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates
-
-
?
mitogen-activated protein kinase kinase 6 + H2O
?
-
specifically cleaves the aminoterminal 7 amino acids of mitogen-activated protein kinase kinases
-
-
?
mitogen-activated protein kinase kinase 6 + H2O
?
-
all but one of the mitogen-activated protein kinase kinases (MEK) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates
-
-
?
mitogen-activated protein kinase kinase 7 + H2O
?
-
specifically cleaves the aminoterminal 7 amino acids of mitogen-activated protein kinase kinases
-
-
?
mitogen-activated protein kinase kinase 7 + H2O
?
-
all but one of the mitogen-activated protein kinase kinases (MEK) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates
-
-
?
additional information
?
-
the enzyme does not degrade mitogen-activated protein kinase kinase 7, Erk1/2, p38 and JNK1/2
-
-
?
additional information
?
-
-
the enzyme does not degrade mitogen-activated protein kinase kinase 7, Erk1/2, p38 and JNK1/2
-
-
?
additional information
?
-
-
cleavage occurs within the N-terminal proline-rich regions of MAPKKs, consensus motifs
-
-
?
additional information
?
-
-
lethal factor acts directly on T and B lymphocytes, blocking antigen receptor-dependent proliferation, cytokine production and Ig production. In this manner, lethal factor mounts a broad-based attack on host-immunity, thus providing Bacillus anthracis with multiple mechanisms for avoiding protective host responses
-
-
?
additional information
?
-
-
participates in the activation of caspase-1
-
-
?
additional information
?
-
-
anthrax lethal factor cleaves and inactivates extracellular signal-regulated kinase kinases of the mitogen-activated protein kinase pathway in human dermal microvascular endothelial cells
-
-
?
additional information
?
-
-
lethal toxin treatment of murine J774A.1 macrophages results in caspase-1 recruitment to the Nalp1b-containing complex, concurrent with processing of cytosolic caspase-1 substrates. Nalp1b belongs to the NLR family of intracellular surveillance proteins, which are able to recognize pathogen-associated molecular patterns, including lipopolysaccharide (LPS). Nalp1b and caspase-1 are able to interact with each other
-
-
?
additional information
?
-
-
prevention of inflammatory response of immune system by preventing interleukin-8 expression: selective blocking of histone H3 phosphorylation at serine 10 and acetylation at lysine 14, H3 normally promotes the accessibility of NF-kappaB (transcription factor for inflammatory gene expression) to target promoters, the histone blocking is mitigated by cleaving mitogen-activated protein kinase kinase, thus preventing the activation of p38-mitogen-activated protein kinase and extracellular signal-regulated kinase
-
-
?
additional information
?
-
-
lethal factor cleaves it substrates between P1 and P1 and has a broad specificity with preference toward hydrophobic residues, but not charged or branched residues. The most preferred residues are, from P1 to P3, Trp, Leu, Met, Tyr, Pro, and Leu
-
-
?
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
NACHT leucine-rich repeat and pyrin domain-containing protein 1B + H2O
?
-
-
-
?
mitogen-activated protein kinase + H2O
?
-
cleavage within N-terminus of MAPKKs
-
-
?
mitogen-activated protein kinase + H2O
?
-
inactivation of substrate
-
-
?
additional information
?
-
-
lethal factor acts directly on T and B lymphocytes, blocking antigen receptor-dependent proliferation, cytokine production and Ig production. In this manner, lethal factor mounts a broad-based attack on host-immunity, thus providing Bacillus anthracis with multiple mechanisms for avoiding protective host responses
-
-
?
additional information
?
-
-
anthrax lethal factor cleaves and inactivates extracellular signal-regulated kinase kinases of the mitogen-activated protein kinase pathway in human dermal microvascular endothelial cells
-
-
?
additional information
?
-
-
lethal toxin treatment of murine J774A.1 macrophages results in caspase-1 recruitment to the Nalp1b-containing complex, concurrent with processing of cytosolic caspase-1 substrates. Nalp1b belongs to the NLR family of intracellular surveillance proteins, which are able to recognize pathogen-associated molecular patterns, including lipopolysaccharide (LPS). Nalp1b and caspase-1 are able to interact with each other
-
-
?
additional information
?
-
-
prevention of inflammatory response of immune system by preventing interleukin-8 expression: selective blocking of histone H3 phosphorylation at serine 10 and acetylation at lysine 14, H3 normally promotes the accessibility of NF-kappaB (transcription factor for inflammatory gene expression) to target promoters, the histone blocking is mitigated by cleaving mitogen-activated protein kinase kinase, thus preventing the activation of p38-mitogen-activated protein kinase and extracellular signal-regulated kinase
-
-
?
additional information
?
-
-
lethal factor cleaves it substrates between P1 and P1 and has a broad specificity with preference toward hydrophobic residues, but not charged or branched residues. The most preferred residues are, from P1 to P3, Trp, Leu, Met, Tyr, Pro, and Leu
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Co2+ is capable to reactivate the apoprotein of lethal factor to a level comparable to that noted for the native zinc enzyme. Co2+-substituted lethal factor is not capable of killing RAW 264.7 murine macrophage-like cells
Cu2+
Mn2+
Co2+ is capable to reactivate the apoprotein of lethal factor to a level comparable to that noted for the native zinc enzyme. Co2+-substituted lethal factor is not capable of killing RAW 264.7 murine macrophage-like cells
Ni2+
Co2+ is capable to reactivate the apoprotein of lethal factor to a level comparable to that noted for the native zinc enzyme. Co2+-substituted lethal factor is not capable of killing RAW 264.7 murine macrophage-like cells
Zn2+
Ca2+
-
activation ability of divalent ions decreases in the follwing order: Zn2+ Ca2+ Mn2+ Mg2+, with Mg2+ completely unable to activate the enzyme
Co2+
-
Co2+ is capable of directly replacing lethal factors active site Zn2+ to yield a hyperactive enzyme with 2fold higher kcat value and about 2.5fold increased catalytic efficiency
Mn2+
-
activation ability of divalent ions decreases in the follwing order: Zn2+ Ca2+ Mn2+ Mg2+, with Mg2+ completely unable to activate the enzyme
Zn2+
Cu2+
Cu2+-substituted lethal factor, prepared by direct exchange and by apoprotein reconstitution methodologies, displays a several-fold higher catalytic competence towards chromogenic and fluorogenic lethal factor substrates than native lethal factor. Cu2+ is bound tightly with a dissociation constant in the femtomolar range. The protein-bound metal ion is coordinated to two nitrogen donor atoms, suggesting that Cu2+ binds to both active site histidine residues. Cu2+-substituted lethal factor is capable of killing RAW 264.7 murine macrophage-like cells
Cu2+
replacement of Zn2+ by Cu2+ leads to an almost 30fold enhancement of the enzyme activity
Zn2+
content is 1 mole per mole of protein. Zinc content is retained upon acidification up to a pH value of 5.5. At pH 5.3, release of about 40% of zinc, and below pH 4.5, sharp increase in the release of zinc
Zn2+
Zn2+-substituted lethal factor is capable of killing RAW 264.7 murine macrophage-like cells
Zn2+
-
lethal factor along with its receptor-binding partner protective antigen, forms lethal toxin, a critical virulence factor for bacillus anthracis. Lethal factor is a Zn2+ protease
Zn2+
-
activation ability of divalent ions decreases in the follwing order: Zn2+ Ca2+ Mn2+ Mg2+, with Mg2+ completely unable to activate the enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-2-[(4-fluoro-3-methoxybenzene-1-sulfonyl)(2-methylpropyl)amino]-N-hydroxy-3-methylbutanamide
-
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)(2-methylpropyl)amino]-N-hydroxy-3-methylbutanamide
-
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)[(4-nitrophenyl)methyl]amino]-N-hydroxypropanamide
-
(2S)-2-(3,4-dichlorophenyl)-N-hydroxy-3-(3-methylphenyl)propanamide
-
(2S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-[[1-(4-fluorophenyl)propyl]amino]-N-hydroxyhexanamide
i.e. PT-8541
(2S)-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-6-[[1-(4-fluorophenyl)propyl]amino]-N-hydroxyhexanamide
i.e. PT-8420
(2S)-6-[(1R)-N-1-(4-fluorophenyl)propan]aminoamino-2-(4-fluoro-3,5-dimethylbenzyl)-N-hydroxyhexanamide
inhibitor provides protection against lethal infection when administered as a monotherapy. Two doses (10 mg/kg) administered at 2 h and 8 h after spore infection are sufficient to provide a significant survival benefit in infected mice
(2S)-6-[(4-fluorobenzyl)amino]-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide
i.e. LFI4
(2S)-6-[N-1-(4-fluorophenyl)propan]amino-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide
inhibitor provides protection against lethal infection when administered as a monotherapy. Two doses (10 mg/kg) administered at 2 h and 8 h after spore infection are sufficient to provide a significant survival benefit in infected mice
1,4-dihydroxy-10-methoxy-5,8-dimethyl-3,7-dioxo-1,3-dihydro-7H-2,6,12-trioxabenzo[5,6]cyclohepta[1,2-e]indene-11-carbaldehyde
i.e. stictic acid
1-[([1,1'-biphenyl]-4-yl)methyl]-3-hydroxy-2-methylpyridine-4(1H)-thione
i.e. 94G5
3-(benzyloxy)-1-(3,4-dichlorobenzene-1-sulfonyl)-N-hydroxypyrrolidine-2-carboxamide
-
3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide
inhibitor used for structure-based pharmacopore model
4-methyl-N-[(1R)-1-[5-(naphthalen-1-yl)-2-(prop-2-en-1-yl)tetrahydrofuran-3-yl]ethyl]benzenesulfonamide
i.e. SM157, non-competitive inhibition
-
5-[4-[(E)-2-[(2R,3R,3'R)-3'-(3,5-dihydroxyphenyl)-6'-hydroxy-2,2'-bis(4-hydroxyphenyl)-2,2',3,3'-tetrahydro-3,4'-bi-1-benzofuran-5-yl]ethenyl]-6-hydroxy-2-(3-hydroxyphenyl)-2,3-dihydro-1-benzofuran-3-yl]benzene-1,3-diol
-
In2LF
i.e. Ac-Gly-Tyr-betaAla-(L-Arg)8-Val-Leu-Arg-CONHOH, competitive inhibitor
N,N'-bis(4-amino-2-methylquinolin-6-yl)urea
i.e. NSC12155, competitive inhibition
N-2-benzyl-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
-
N-2-[4-(aminomethyl)benzyl]-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
-
N-hydroxy-N2-[[3-(methoxymethyl)phenyl]sulfonyl]-N2-(2-methylpropyl)-D-valinamide
-
N-[([1,1'-biphenyl]-4-yl)methyl]-3-hydroxy-4-sulfanylidene-4H-pyran-2-carbothioamide
-
N-[([1,1'-biphenyl]-4-yl)methyl]-3-hydroxy-6-methyl-4-sulfanylidene-4H-pyran-2-carboxamide
i.e. AM-2S
N-[3-(1,3-benzothiazol-2-yl)-4-methylthiophen-2-yl]-4-chlorobenzene-1-sulfonamide
-
N-[3-(1,3-benzothiazol-2-yl)thiophen-2-yl]-4'-methoxy[1,1'-biphenyl]-4-sulfonamide
-
N2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-N-2-(4-nitrobenzyl)-D-alaninamide
-
(1E,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
-
-
(1Z,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
-
-
(2R)-N4-hydroxy-N1-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
-
inhibitor identified by in silico high-throughput virtual screening protocol
(3S)-N-hydroxy-4-methyl-3-([[(2R)-1-(methylamino)-1-oxo-4-phenylbutan-2-yl]amino]methyl)pentanamide
-
inhibitor identified by in silico high-throughput virtual screening protocol
(5E)-5-(1,3-benzothiazol-2-ylimino)-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
-
-
(5Z)-3-(4-hydroxyphenyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-3-(4-methoxyphenyl)-2-thioxo-5-([5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-1,3-thiazolidin-4-one
-
-
(5Z)-3-(furan-2-ylmethyl)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-3-(furan-2-ylmethyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-(furan-2-ylmethyl)-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[[5-(4-fluorophenyl)furan-2-yl]methylidene]-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-4-one
-
-
1-[(1S,2R,3S,4S,6S)-2-amino-6-[(6-amino-2,6-dideoxy-a-D-arabino-hexopyranosyl)oxy]-3,4-dihydroxycyclohexyl]guanidine
-
-
2-([benzyl(ethyl)amino]methyl)-6-iodo-4-methylphenol
-
inhibitor identified by in silico high-throughput virtual screening protocol
2-chloro-4-(5-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-2-yl)benzoic acid
-
-
2-chloro-4-(5-[(Z)-[4-oxo-3-(pyridin-3-ylmethyl)-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
-
-
2-chloro-4-[5-[(Z)-(4-oxo-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
-
-
2-chloro-4-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl]sulfamoyl]benzoic acid
-
-
2-chloro-5-[(4Z)-3-methyl-4-[[4-(1-methylethyl)phenyl]methylidene]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
-
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
-
2-chloro-5-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenylimidazolidin-1-yl]sulfamoyl]benzoic acid
-
-
2-hydroxy-5-(5-[(Z)-[2-imino-4-oxo-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
-
-
2-hydroxy-5-[5-[(Z)-[2-imino-3-[imino(methylsulfanyl)methyl]-4-oxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
-
-
2-[[(2-amino-2-carboxyethyl)sulfanyl]methyl]-5-phenylfuran-3-carboxylic acid
-
-
3,4-dihydroxy-N'-[(1Z)-(2-hydroxy-5-nitrophenyl)methylidene]benzohydrazide
-
-
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
-
-
3-[(5E)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
3-[(5Z)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
3-[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
3-[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
3-[(5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
4-(5-[(Z)-[3-(4-nitrophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
-
-
4-phenylaminocarbonylbis-demethoxycurcumin
-
inhibitory potency is comparable with curcumin, while showing improved solubility and stability
4-[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
-
-
4-[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
-
-
4-[5-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxopyridin-3(6H)-ylidene)methyl]furan-2-yl]benzenesulfonamide
-
-
4-[5-[(Z)-(3-benzyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
-
-
4-[5-[(Z)-[4-oxo-2-thioxo-3-[3-(trifluoromethyl)phenyl]-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
-
-
4-[[(4-chlorophenyl)carbamoyl]amino]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
-
-
5-(4-carboxy-3-chlorophenyl)-2-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-3-carboxylic acid
-
-
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
-
-
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]uran-2-yl)benzoic acid
-
-
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
-
-
8-[(E)-[[4-(2,3-dihydro-1,3-thiazol-2-ylsulfamoyl)phenyl]imino]methyl]-4H-1,3-benzodioxine-6-carboxylic acid
-
-
C-terminal dimer of the protective antigen binding domain of anthrax lethal factor
-
-
-
C-terminal trimer of the protective antigen binding domain of anthrax lethal factor
-
-
-
celastrol
-
celastrol, a quinine methide triterpene derived from a plant extract used in herbal medicine, inhibits lethal toxin-induced death of RAW264.7 murine macrophages. Celastrol does not prevent cleavage of mitogen activated protein kinase kinase 1. Celastrol confers almost complete protection when it is added up to 1.5 h after intoxication, indicating that it can rescue cells in the late stages of intoxication. Celastrol inhibits the proteasome-dependent degradation of proteins in RAW264.7 cells. Celastrol blocks stimulation of IL-18 processing, indicating that celastrol acts upstream of inflammasome activation
curcumin
-
inhibits by both decreasing catalytic capacity and increasing substrate affinity
fluvastatin
-
statins attenuate lethal factor action action. statin treatment maintains macrophage cell viability above 60% of untreated control cells even after 9 h of lethal toxin treatment. Statins decrease mitogen-activated protein kinase cleavage
mevastatin
-
statins attenuate lethal factor action action. statin treatment maintains macrophage cell viability above 60% of untreated control cells even after 9 h of lethal toxin treatment. Statins decrease mitogen-activated protein kinase cleavage
N'1,N'4-bis[(1E)-(2-hydroxy-5-methylphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
-
N'1-[(1E)-(2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
-
N'1-[(1E)-(5-fluoro-2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(5-fluoro-2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
-
N,N''',N'''''',N'''''''''-[[(1R,3S,4S,6R)-4,6-dicarbamimidamidocyclohexane-1,3-diyl]bis(oxybenzene-1,2,4-triyl)]tetraguanidine
-
-
N,N'''-[(1R,3S)-4-(2,4-dicarbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S)-4-(2-amino-1H-benzimidazol-7-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4R,5R,6S)-4-[(2,6-dicarbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-5,6-dihydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4R,6R)-4-(2-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4S,6R)-4-(3-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4S,6R)-4-(5-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1S,2R,3S,4S,6S)-6-[(6-amino-2-carbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-3,4-dihydroxycyclohexane-1,2-diyl]diguanidine
-
-
N,N'''-[4-[(1R,2S,4R,5R)-2,4-dicarbamimidamido-5-hydroxycyclohexyl]benzene-1,3-diyl]diguanidine
-
-
N-terminal dimer of the protective antigen binding domain of anthrax lethal factor
-
-
-
N-terminal trimer of the protective antigen binding domain of anthrax lethal factor
-
-
-
NH4Cl
-
blocks mitogen-activated protein kinase kinase 3 proteolysis in anthrax lethal toxin-treated macrophages
simvastatin
-
statins attenuate lethal factor action action. statin treatment maintains macrophage cell viability above 60% of untreated control cells even after 9 h of lethal toxin treatment. Statins decrease mitogen-activated protein kinase cleavage
verapamil
-
blocks mitogen-activated protein kinase kinase 3 proteolysis in anthrax lethal toxin-treated macrophages
[(5Z)-5-([5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3-chloro-4-sulfamoylphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-chloro-2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-iodophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[4-[(5Z)-5-(furan-2-ylmethylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]phenyl]acetic acid
-
-
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)amino]-N-hydroxy-2-(oxan-4-yl)acetamide
-
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)amino]-N-hydroxy-2-(oxan-4-yl)acetamide
i.e. L915
additional information
-
peptides that can block toxin assembly. Minimal peptide sequence TYWWLD can be used to develop potent polyvalent inhibitors of anthrax toxin
-
additional information
-
Ca2+-free medium completely prevents mitogen-activated protein kinase kinase 3 proteolysis in anthrax lethal toxin-treated macrophages
-
additional information
-
complete caspase-1 inhibition is required to block antrax lethal toxin-mediated necrosis
-
additional information
-
statin-mediated effects on lethal toxin action are attributable to disruption of Rho GTPases. The Rho GTPase-inactivating toxin, toxin B, does not significantly affect lethal toxin binding or internalization, suggesting that the Rho GTPases regulate trafficking and/or localization of lethal toxin once internalized
-
additional information
-
fusion protein of N-terminal 27 amino acids deletion of protective antigen-binding domain of anthrax lethal factor Delta27LFn and protective antigen-binding domain of edema factor is a 62-fold more potent toxin inhibitor than protective antigen-binding domain of anthrax lethal factor or protective antigen-binding domain of edema factor in a cell model of intoxication, and this increased activity corresponds to a 39-fold higher protective antigen-binding affinity by Biacore analysis. The fusion protein can protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge
-
additional information
-
micromolar-level anthrax lethal factor inhibition can be attained by compounds with non-hydroxamate zinc-binding groups that exhibit monodentate zinc chelation as long as key hydrophobic interactions with at least two anthrax lethal factor subsites are retained
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
matrix metalloproteinase
-
matrix-metalloproteinase-activated lethal toxin has much lower in vivo toxicity than wild type toxin
-
additional information
-
monoclonal antibodies PA I 3F3-2-2, PA 2II 2F9-1-1, and PA I 6C3-1-1, directed against protective antigen of Bacillus anthracis, enhance lethal toxin activity in vivo
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0023 - 0.0042
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
0.0016 - 0.0019
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
0.073
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide
pH 7.4, 22°C, apoprotein reconstituted in presence of Zn2+
0.0086
fluorescence resonance energy transfer peptide MAPKKide
-
in 20 mM HEPES, pH 7.4, at 25°C
-
0.0023
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
copper-substituted enzyme, at pH 6.5 and 20°C
0.0042
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
copper-substituted enzyme, at pH 6.5 and 20°C
0.0016
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
copper-substituted enzyme, at pH 6.5 and 20°C
0.0019
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
copper-substituted enzyme, at pH 6.5 and 20°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
10.6 - 26.6
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
3.9 - 6.1
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
21.2
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide
pH 7.4, 22°C, apoprotein reconstituted in presence of Cu2+
10.6
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
copper-substituted enzyme, at pH 6.5 and 20°C
26.6
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
copper-substituted enzyme, at pH 6.5 and 20°C
3.9
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
copper-substituted enzyme, at pH 6.5 and 20°C
6.1
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
copper-substituted enzyme, at pH 6.5 and 20°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4660 - 6360
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
2070 - 3810
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
2900
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide
pH 7.4, 22°C, apoprotein reconstituted in presence of Zn2+
4660
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
copper-substituted enzyme, at pH 6.5 and 20°C
6360
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-4-nitroanilide
copper-substituted enzyme, at pH 6.5 and 20°C
2070
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
copper-substituted enzyme, at pH 6.5 and 20°C
3810
acetyl-Gly-Tyr-beta-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Val-Leu-Arg-7-amido-4-methylcoumarin
copper-substituted enzyme, at pH 6.5 and 20°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000000042
(2S)-6-[(1R)-N-1-(4-fluorophenyl)propan]aminoamino-2-(4-fluoro-3,5-dimethylbenzyl)-N-hydroxyhexanamide
pH not specified in the publication, temperature not specified in the publication
0.00000033
(2S)-6-[N-1-(4-fluorophenyl)propan]amino-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide
pH not specified in the publication, temperature not specified in the publication
0.0000003
(D-Arg)9-Trp-Leu-Met-CONHOH
pH and temperature not specified in the publication
0.0092
4-methyl-N-[(1R)-1-[5-(naphthalen-1-yl)-2-(prop-2-en-1-yl)tetrahydrofuran-3-yl]ethyl]benzenesulfonamide
pH and temperature not specified in the publication
-
0.001
N-[3-(1,3-benzothiazol-2-yl)thiophen-2-yl]-4'-methoxy[1,1'-biphenyl]-4-sulfonamide
pH and temperature not specified in the publication
0.0027
(1E,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
-
-
0.0027
(1Z,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
-
-
0.0011
(4E)-4-[(2,4-dihydroxyphenyl)methylidene]-1,2,5-thiadiazolidin-3-one
-
-
0.0042
(5E)-5-(1,3-benzothiazol-2-ylimino)-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
-
-
0.0011
(5Z)-5-[(2,4-dihydroxyphenyl)methylidene]-2-thioxoimidazolidin-4-one
-
-
0.0024
2-chloro-4-(5-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-2-yl)benzoic acid
-
-
0.0025
2-chloro-4-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl]sulfamoyl]benzoic acid
-
-
0.0009
2-chloro-5-[(4Z)-3-methyl-4-[[4-(1-methylethyl)phenyl]methylidene]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
-
0.0021 - 0.0107
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
0.0036
2-chloro-5-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenylimidazolidin-1-yl]sulfamoyl]benzoic acid
-
-
0.0031
2-hydroxy-5-(5-[(Z)-[2-imino-4-oxo-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
-
-
0.0031
2-hydroxy-5-[5-[(Z)-[2-imino-3-[imino(methylsulfanyl)methyl]-4-oxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
-
-
0.0029
2-[[(2-amino-2-carboxyethyl)sulfanyl]methyl]-5-phenylfuran-3-carboxylic acid
-
-
0.0054 - 0.0072
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
0.0033
3-[(5E)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
0.0033
3-[(5Z)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
-
0.0054
4-[5-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxopyridin-3(6H)-ylidene)methyl]furan-2-yl]benzenesulfonamide
-
-
0.0009
4-[[(4-chlorophenyl)carbamoyl]amino]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
-
-
0.0024
5-(4-carboxy-3-chlorophenyl)-2-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-3-carboxylic acid
-
-
0.0016
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
-
-
0.0016
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]uran-2-yl)benzoic acid
-
-
0.0008 - 0.0011
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
0.0018
8-[(E)-[[4-(2,3-dihydro-1,3-thiazol-2-ylsulfamoyl)phenyl]imino]methyl]-4H-1,3-benzodioxine-6-carboxylic acid
-
-
0.000032
[(5Z)-5-([5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
0.0021
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
-
0.0107
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
-
0.0054
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
-
-
0.0072
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
-
-
0.0008
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
-
-
0.0011
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.267
(2R)-2-[(4-fluoro-3-methoxybenzene-1-sulfonyl)(2-methylpropyl)amino]-N-hydroxy-3-methylbutanamide
Bacillus anthracis
pH and temperature not specified in the publication
0.09
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)(2-methylpropyl)amino]-N-hydroxy-3-methylbutanamide
Bacillus anthracis
pH and temperature not specified in the publication
0.0001
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)amino]-N-hydroxy-2-(oxan-4-yl)acetamide
Bacillus anthracis
pH and temperature not specified in the publication
0.0149
(2R)-2-[(4-fluoro-3-methylbenzene-1-sulfonyl)[(4-nitrophenyl)methyl]amino]-N-hydroxypropanamide
Bacillus anthracis
pH and temperature not specified in the publication
0.039
5-[4-[(E)-2-[(2R,3R,3'R)-3'-(3,5-dihydroxyphenyl)-6'-hydroxy-2,2'-bis(4-hydroxyphenyl)-2,2',3,3'-tetrahydro-3,4'-bi-1-benzofuran-5-yl]ethenyl]-6-hydroxy-2-(3-hydroxyphenyl)-2,3-dihydro-1-benzofuran-3-yl]benzene-1,3-diol
Bacillus anthracis
pH and temperature not specified in the publication
0.0015
N-(4-amino-2-methylquinolin-6-yl)-3-(2-methoxyphenyl)propanamide
Bacillus anthracis
pH and temperature not specified in the publication
0.003
N-(4-amino-2-methylquinolin-6-yl)-4-(quinolin-6-yl)benzamide
Bacillus anthracis
pH and temperature not specified in the publication
0.0152
N-2-benzyl-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
Bacillus anthracis
pH not specified in the publication, temperature not specified in the publication
0.0056
N-2-[4-(aminomethyl)benzyl]-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
Bacillus anthracis
pH not specified in the publication, temperature not specified in the publication
0.95
N-hydroxy-N2-[[3-(methoxymethyl)phenyl]sulfonyl]-N2-(2-methylpropyl)-D-valinamide
Bacillus anthracis
pH and temperature not specified in the publication
0.0149
N2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-N-2-(4-nitrobenzyl)-D-alaninamide
Bacillus anthracis
pH not specified in the publication, temperature not specified in the publication
0.003
(1E,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
Bacillus anthracis
-
-
0.003
(1Z,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
Bacillus anthracis
-
-
0.0102
(2R)-N4-hydroxy-N1-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
Bacillus anthracis
-
pH 8.0, 37°C
0.0071
(3S)-N-hydroxy-4-methyl-3-([[(2R)-1-(methylamino)-1-oxo-4-phenylbutan-2-yl]amino]methyl)pentanamide
Bacillus anthracis
-
pH 8.0, 37°C
0.0034
(4E)-4-[(2,4-dihydroxyphenyl)methylidene]-1,2,5-thiadiazolidin-3-one
Bacillus anthracis
-
-
0.0077
(5E)-5-(1,3-benzothiazol-2-ylimino)-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
Bacillus anthracis
-
-
0.0377
(5Z)-3-(4-hydroxyphenyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.3
(5Z)-3-(4-methoxyphenyl)-2-thioxo-5-([5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0383
(5Z)-3-(furan-2-ylmethyl)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0126
(5Z)-3-(furan-2-ylmethyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0034
(5Z)-5-[(2,4-dihydroxyphenyl)methylidene]-2-thioxoimidazolidin-4-one
Bacillus anthracis
-
-
0.0319
(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0074
(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.007
(5Z)-5-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.15
(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-(furan-2-ylmethyl)-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.05
(5Z)-5-[[5-(4-fluorophenyl)furan-2-yl]methylidene]-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0007
1-[(1S,2R,3S,4S,6S)-2-amino-6-[(6-amino-2,6-dideoxy-a-D-arabino-hexopyranosyl)oxy]-3,4-dihydroxycyclohexyl]guanidine
Bacillus anthracis
-
-
0.0495
2-([benzyl(ethyl)amino]methyl)-6-iodo-4-methylphenol
Bacillus anthracis
-
pH 8.0, 37°C
0.0042
2-chloro-4-(5-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0099
2-chloro-4-(5-[(Z)-[4-oxo-3-(pyridin-3-ylmethyl)-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0027
2-chloro-4-[5-[(Z)-(4-oxo-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0036
2-chloro-4-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl]sulfamoyl]benzoic acid
Bacillus anthracis
-
-
0.0079
2-chloro-5-[(4Z)-3-methyl-4-[[4-(1-methylethyl)phenyl]methylidene]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
Bacillus anthracis
-
-
0.0021 - 0.0107
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
0.0025
2-chloro-5-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenylimidazolidin-1-yl]sulfamoyl]benzoic acid
Bacillus anthracis
-
-
0.0048
2-hydroxy-5-(5-[(Z)-[2-imino-4-oxo-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0048
2-hydroxy-5-[5-[(Z)-[2-imino-3-[imino(methylsulfanyl)methyl]-4-oxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0036
2-[[(2-amino-2-carboxyethyl)sulfanyl]methyl]-5-phenylfuran-3-carboxylic acid
Bacillus anthracis
-
-
0.2
3,4-dihydroxy-N'-[(1Z)-(2-hydroxy-5-nitrophenyl)methylidene]benzohydrazide
Bacillus anthracis
-
DS-998
0.0083 - 0.0105
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
0.0044
3-[(5E)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0044
3-[(5Z)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0128
3-[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0008
3-[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0027
3-[(5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0048
4-(5-[(Z)-[3-(4-nitrophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.02
4-[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
Bacillus anthracis
-
-
0.0023
4-[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
Bacillus anthracis
-
-
0.0083
4-[5-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxopyridin-3(6H)-ylidene)methyl]furan-2-yl]benzenesulfonamide
Bacillus anthracis
-
-
0.006
4-[5-[(Z)-(3-benzyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0029
4-[5-[(Z)-[4-oxo-2-thioxo-3-[3-(trifluoromethyl)phenyl]-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0039
4-[[(4-chlorophenyl)carbamoyl]amino]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
Bacillus anthracis
-
-
0.0042
5-(4-carboxy-3-chlorophenyl)-2-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-3-carboxylic acid
Bacillus anthracis
-
-
0.0017
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0017
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]uran-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0008
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0093
8-[(E)-[[4-(2,3-dihydro-1,3-thiazol-2-ylsulfamoyl)phenyl]imino]methyl]-4H-1,3-benzodioxine-6-carboxylic acid
Bacillus anthracis
-
-
0.08
N'1,N'4-bis[(1E)-(2-hydroxy-5-methylphenyl)methylidene]benzene-1,4-dicarbohydrazide
Bacillus anthracis
-
-
0.05
N'1-[(1E)-(2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
Bacillus anthracis
-
-
0.05
N'1-[(1E)-(5-fluoro-2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(5-fluoro-2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
Bacillus anthracis
-
-
0.00065
N,N''',N'''''',N'''''''''-[[(1R,3S,4S,6R)-4,6-dicarbamimidamidocyclohexane-1,3-diyl]bis(oxybenzene-1,2,4-triyl)]tetraguanidine
Bacillus anthracis
-
-
0.0107
N,N'''-[(1R,3S)-4-(2,4-dicarbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.1537
N,N'''-[(1R,3S)-4-(2-amino-1H-benzimidazol-7-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0007
N,N'''-[(1R,3S,4R,5R,6S)-4-[(2,6-dicarbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-5,6-dihydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0306
N,N'''-[(1R,3S,4R,6R)-4-(2-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0314
N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0149
N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0041
N,N'''-[(1R,3S,4S,6R)-4-(3-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0066
N,N'''-[(1R,3S,4S,6R)-4-(5-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0005
N,N'''-[(1S,2R,3S,4S,6S)-6-[(6-amino-2-carbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-3,4-dihydroxycyclohexane-1,2-diyl]diguanidine
Bacillus anthracis
-
-
0.0006
N,N'''-[4-[(1R,2S,4R,5R)-2,4-dicarbamimidamido-5-hydroxycyclohexyl]benzene-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0031
[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.000265
[(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.000298
[(5Z)-5-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0091
[(5Z)-5-[[5-(3-chloro-4-sulfamoylphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0031
[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.00085
[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0005
[(5Z)-5-[[5-(4-chloro-2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0009
[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0055
[(5Z)-5-[[5-(4-iodophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.14
[4-[(5Z)-5-(furan-2-ylmethylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]phenyl]acetic acid
Bacillus anthracis
-
-
0.0021
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
Bacillus anthracis
-
-
0.0107
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
Bacillus anthracis
-
-
0.0083
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.8
progressive further loss of activity. Biphasic loss of activity upon acidification
6.7
about 60% of maximum activity. Biphasic loss of activity upon acidification
7 - 8.5
the enzyme degrades R9LF-1 with maximum efficiency in the pH range of 7.0-8.5, which correlates well with the range of enzymatic activity with its native substrate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
anthrax lethal toxin binds and enters murine neutrophils
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins including lethal factor
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
about 30% demetallation is observed at pH values close to those found in late endosomes. A substantial proportion of lethal factor molecules may not be in their zinc-bound state prior to translocation
physiological function
physiological function
physiological function
in a murine model of intoxication, lethal factor causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. The pathology correlates with a blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. Treated mice nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. Intestinal pathology depends upon lethal factor proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics
physiological function
high glucose-induced activation of the MAPK extracellular signal-regulated kinase (ERK1/2) and p38 in the ARPE cell line is blocked by the enzyme. High glucose induced ARPE cells over proliferation is inhibited by the enzyme
physiological function
the enzyme rapidly reduces c-Jun levels by inhibiting c-Jun gene transcription and promoting c-Jun protein degradation
physiological function
-
secreted type-IIA phospholipase A2sPLA2-IIA expression is induced via a sequential MAPK-NF-kappaB activation and anthrax lethal toxin inhibits this expression likely by interfering with the transactivation of NF-kappaB in the nucleus. Anthrax lethal toxin inhibits IL-1b-induced p38 phosphorylation as well as sPLA2-IIA promoter activity in CHO cells. Inhibition of sPLA2-IIA promoter activity is mimicked by co-transfection with dominant negative construct of p38 and reversed by the active form of p38-MAPK. Both anthrax lethal toxin and the dominant negative construct of p38 decrease IL-1b-induced NF-kappaB luciferase activity. Neither anthrax lethal toxin nor specific p-38 inhibitor interfere with LPS-induced IkappaBalpha degradation or NF-kappaB nuclear translocation in guinea pig alveolar macrophages. Subcutaneous administration of anthrax lethal toxin to guinea pig before LPS challenge reduces sPLA2-IIA levels in broncho-alveolar lavages and ear
physiological function
-
the anthrax toxin triggers tyrosine phosphorylation of its own receptors, capillary morphogenesis gene 2 and tumor endothelial marker 8, which is required for efficient toxin uptake. Phosphorylation of the receptors is dependent on src-like kinases, which are activated upon toxin binding. src-Dependent phosphorylation of the receptor is required for its subsequent ubiquitination, which in turn is required for clathrin-mediated endocytosis. Uptake of the anthrax toxin and processing of the lethal factor substrate MEK1 are inhibited by silencing of src and fyn, as well as in src and fyn knockout cells
physiological function
-
the cytoplasmic delivery of anthrax lethal factor by anthrax toxin receptor ANTXR2 is mediated by cathepsin B and requires lysosomal fusion with anthrax lethal toxin containing endosomes. Binding of protective antigen to ANXTR1 or -2 triggers autophagy, which facilitates the cytoplasmic delivery of ANTXR2-associated anthrax lethal factor. Whereas cells treated with the membrane-permeable cathepsin B inhibitor CA074-Me- orcathepsin B-deficient cells have no defect in fusion of light chain 3-containing autophagic vacuoles with lysosomes, autophagic flux is significantly delayed
physiological function
-
translocation of anthrax lethal factor protective antigen-binding domain LFN through the protective antigen pore is triggered by pH gradient. Residues 14-28 at the N-terminus of LFN are required for LFN to inhibit ion conductance through the pore. The translocation of substrate proteins through the protective antigen pore is dependent on the presence of both acidic and basic residues in the unstructured N-terminal region
physiological function
-
anthrax lethal factor of Bacillus anthracis is a major factor for lethality of anthrax infection
physiological function
-
anthrax lethal toxin disrupts endothelial, intestinal epithelial, alveolar-endothelial and blood brain barriers of the host
physiological function
-
anthrax lethal toxin is a virulence factor of Bacilillus anthracis that is a bivalent toxin, containing lethal factor and protective Ag proteins, which causes cytotoxicity and altered macrophage function. Anthrax lethal toxin exposure results in early K+ efflux from macrophages associated with caspase-1 activation and increased interleukin-1beta release
physiological function
-
in lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Coordinated disruption of the Rab11/Sec15 exocyst by anthrax toxins may contribute to toxin-dependent barrier disruption and vascular dysfunction during Bacillus anthracis infection. LF and EF synergistically inhibit Notch signaling and inhibit Rab11/Sec15-dependent recycling
physiological function
-
lethal toxin (LeTx) containing lethal factor is the major virulence factor contributing to anthrax. LeTx-mediated MAPKK inhibition alters endothelial cell function
physiological function
-
the Lethal Toxin is formed when up to three molecules of lethal factor bind a 63 kDA protective antigen heptamer. Anthrax lethal toxin is a major virulence factor of Bacillus anthracis. Fully assembled lethal toxin binds an anthrax toxin receptor with almost 100fold higher affinity than the protective antigen alone
physiological function
-
treatment of rat pulmonary microvascular endothelial cells with anthrax lethal toxin (LeTx) increases endothelial barrier permeability and gap formation between endothelial cells through disrupting p38 signaling. LeTxr educes phosphorylation of p38, MAP kinase 2, and HSP27
physiological function
-
in mice treated with Anthrax lethal factor, serum lactate levels are reduced. Lethal factor inhibits the accumulation of hypoxia-inducible factor HIF-1alpha, a subunit of HIF-1, the master regulator directing cellular responses to hypoxia. The toxin has no effect on the transcription or protein turnover of HIF-1LPH, but inhibits HIF-1alpha translation. Lethal factor treatment diminishes phosphorylation of eIF4B, eIF4E, and rpS6, critical components of the intracellular machinery required for HIF-1alpha translation. Lethal factor treatment decreases the survival of hepatocyte cell lines grown in hypoxic conditions, an effect that is overcome by preinduction of HIF-1alpha
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
90000
1 * 90000, the protein is monomeric in solution, based on gel filtration
90000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
monomer
1 * 90000, the protein is monomeric in solution, based on gel filtration
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with inhibitor 3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide, structure is used for pharmacopore model
in complex with inhibitors N-2-benzyl-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide, N2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-N-2-(4-nitrobenzyl)-D-alaninamide, N-2-[4-(aminomethyl)benzyl]-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide to 2.2-2.5 A resolution. Identification of frequently populated conformational states termed bioactive, open and tight. The bioactive position is observed with large substrate peptides and leaves all peptide-recognition subsites open and accessible. The tight state is seen in unliganded and small-molecule complex structures. In this state, domain 3 is clamped over certain substrate subsites, blocking access. The open position appears to be an intermediate state between these extremes and is observed owing to steric constraints imposed by specific bound ligands
structural analyzation by NMR-spectroscopy leading to 96% assignment of the backbone amides and overall assignment of 1HN, 15N, 13Calpha, 13Cbeta and 13C' chemical shifts to 85%
docking and molecular dynamics calculations to examine the anthrax lethal factor-MEK/MKK interaction along the catalytic channel up to a distance of 20 A from the zinc atom. The Zn-bound water molecule is predicted to form hydrogen bonds with the carbonyl oxygen of Ile, i.e. P1' of substrates MEK1, MKK3b, Leu, ie. P1' of substrate MKK4-1, and Leu, ie. P2 of substrate MKK6b as well as with the hydroxyl group of Thr, i.e. P2' of substrate MKK4-2. This hydrogen bond is an additional contact to the already existing polarization of the carbonyl oxygen between Zn and Glu687 carboxylate
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E269A
the mutant shows strongly increased cleavage ability for mitogen-activated protein kinase kinase-1 and reduced activity with mitogen-activated protein kinase kinase-6 compared to the wild type enzyme
E539R
the mutant shows slightly increased cleavage ability for mitogen-activated protein kinase kinase-1 and reduced activity with mitogen-activated protein kinase kinase-6 compared to the wild type enzyme
L259A
the mutant cleaves MEK1 about 2fold less efficiently than the wild type enzyme
L431A
the mutant shows slightly increased cleavage ability for mitogen-activated protein kinase kinase-6 compared to the wild type enzyme
M264A
the mutant cleaves MEK1 2.5fold less efficiently than the wild type enzyme
R263A
the mutant shows reduced cleavage ability for mitogen-activated protein kinase kinase-1 compared to the wild type enzyme
R491E
the mutant cleaves MEK1 about 2fold less efficiently than the wild type enzyme
W271A
the mutation completely abolishes cleavage ability of mitogen-activated protein kinase kinase-6 but has no effect on the ability to cleave MEK1. The mutant blocks ERK phosphorylation and growth in a melanoma cell line, suggesting that it may provide a highly selective inhibitor of MEK1/2 for use as a cancer therapeutic
Y268A
the mutant cleaves MEK1 6fold less efficiently than the wild type enzyme
H690A
K518E/E682G
-
mutation in anthrax lethal factor, mutant is defective at causing pyroptosis in RAW 264.7 cells and at activating the Nlrp1b inflammasome in a heterologous expression system. LF-K518E /E682G does not exhibit an overall impairment of function and LF-K518E /E682G efficiently kills melanoma cells
additional information
additional information
-
effects of anthrax lethal toxin on human primary keratinocytes are investigated. Cells are resistant to LeTx-triggered cytotoxicity, even though all the MEK (MEK1 through 7), except MEK5, are cleaved in these cells. Over the 24 h time course of the study, the levels of two pro-inflammatory molecules, interleukin-6 and granulocyte-macrophage colony stimulating factor (GM-CSF), decline, but the production of RANTES, a known chemoattractant for multiple types of immune cells, increases
additional information
-
in order to examine the role of protective antigen a lethal factor (LFn) fusion protein bearing two epitopes from Ova, one restricted by MHC-II and one restricted by MHC-I is generated. This single LFn fusion protein is capable of stimulating both ovalbumin-specific CD4+ and ovalbumin-specific CD8+ T-cell responses in mice
additional information
-
intranasal instillationin a mouse model of pulmonary anthrax of a Bacillus anthracis strain RPLC2 bearing inactive lethal toxin (double mutant) lethal toxin stimulates cytokine production (IL-6 and KC, mouse orthologue of IL-8) and polymorphonuclear neutrophils recruitment in lungs. These responses are repressed by a prior instillation of an lethal toxin preparation. In contrast, instillation of a Bacillus anthracis strain expressing active lethal toxin represses lung inflammation. The inhibitory effects of lethal toxin on cytokine production are associated with an alteration of ERK and p38-MAPK phosphorylation, but not JNK phosphorylation. Although NF-kappaB is essential for IL-8 expression, lethal toxin downregulates this expression without interfering with NF-kappaB activation in epithelial cells. Lethal toxin selectively prevents histone H3 phosphorylation at Ser 10 and recruitment of the p65 subunit of NF-kappaB at the IL-8 and KC promoters
additional information
-
it is investigated whether lethal factor (LFn) fusion proteins and protective antigen can also be used to deliver antigen to the MHC-II pathway for the stimulation of antigen-specific CD4+ T-cells. A CD4+ T-cell epitope from chicken ovalbumin is fused to nontoxic LFn and demonstrates that this recombinant protein induces an ovalbumin-specific CD4+ T-cell response both in vitro and in mice
additional information
-
non-specific furin cleavage sequence (164RKKR167) of the protective antigen of anthrax toxin is substituted by the cleavage sequence for gelatinase class of matrix metalloproteinase (164GPLGMLSQ171) to prevent non-specific action and enhance target specific action in endothelial cells
additional information
-
the responses of various murine dendritic cells to anthrax lethal toxin is investigated: Using a variety of knockout mice, it is shown that depending on the mouse strain, death of bone marrow-derived dendritic cells and macrophages is mediated either by a fast Nalp1b, a member of the NOD-like receptor family, and caspase-1-dependent, or by a slow caspase-1-independent pathway that is triggered by the impairment of MEK1/2 pathways. Caspase-1-independent death is observed in cells of different genetic backgrounds and interestingly occurs only in immature dendritic cells. Maturation, triggered by different types of stimuli, leads to full protection of dendritic cells
additional information
-
construction of fusion protein of the anthrax toxin lethal factor N-terminal domain LFn, residues 1-254, with beta-lactamase
additional information
-
preparation of semisynthetic protective antigen-binding domain of anthrax lethal factor, LFN, by native chemical ligation of synthetic LFN residues 14-28 thioester with recombinant N29C-LFN residues 29-263 and comparison with two variants containing alterations in residues 14-28 of the N-terminal region. An analogue with three positively charged residues and an acetylated N-terminus, blocks ion conductance more efficiently than the control analogue, which lacks charged residues in the N-terminal segment. The semisynthesis platform allows for investigation of the interaction of the pore with its substrates
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
nickel affinity column chromatography and Superdex S200 gel filtration
His-Trap HP nickel column chromatography, ammonium sulfate precipitation, and phenyl-Sepharose column chromatography
the recombinant LFn fusion proteins contain a vector-encoded His6 tag at the amino terminus and are purified by Ni2+-affinity chromatography to greater than 95% purity as determined by Coomassie staining
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
fusion protein between lethal factor and the catalytic domain of diphtheria toxin is expressed in Escherichia coli BL21(DE3) cells
-
recombinant anthrax lethal toxin proteins consisting a model CD4 T-cell epitope from chicken ovalbumin (Ova) fused to nontoxic lethal factor (LFn). The antigen tags are generated by annealing single-stranded DNA oligonucleotides to form double-stranded DNA Plasmids are transformed into Escherichia coli BL21
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
diagnostics
medicine
molecular biology
synthesis
-
preparation of semisynthetic protective antigen-binding domain of anthrax lethal factor, LFN, by native chemical ligation of synthetic LFN residues 14-28 thioester with recombinant N29C-LFN residues 29-263 and comparison with two variants containing alterations in residues 14-28 of the N-terminal region. The properties of the variants in blocking ion conductance through the protective antigen pore and translocating across planar phospholipid bilayers in response to a pH gradient are consistent with current concepts of the mechanism of polypeptide translocation through the pore. The semisynthesis platform allows for investigation of the interaction of the pore with its substrates
medicine
administration of lethal factor proteases early in the infection inhibits dissemination of vegetative bacteria to the organs in the first 32 h following infection. Neutralizing antibodies against edema factor also inhibit bacterial dissemination with similar efficacy
medicine
in a murine model of intoxication, lethal factor causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. The pathology correlates with a blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. Treated mice nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. Intestinal pathology depends upon lethal factor proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics
medicine
seven of eleven acute myeloid leukemia cell lines show cytotoxic responses to anthrax lethal toxin LeTx. Cytotoxicity is mimicked by the specific mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor U0126, indicating involvement of the ERK1/2 branch of the MAPK pathway. The four LeTx-resistant cell lines are sensitive to the phosphatidylinositol 3-kinase inhibitor LY294002. with a lack of additive/synergistic effects when both pathways are inhibited. Phospho-ERK1/2 is only present in LeTx-sensitive cells. LeTx-induced cell death is caspase-independent and nonapoptotic
diagnostics
-
the anthrax lethal toxin neutralization assay (TNA) measures the ability of antibodies to neutralize the cytotoxicity of anthrax lethal toxin rather than quantifying total antibody through a conjugated species-specific secondary antibody. TNA may provide a more relevant immunological measure, as it quantitates functional antibodies only rather than total protective antigen-binding antibodies. In this study, TNA data are generated in several different laboratories to measure the immune responses in rabbits, nonhuman primates, and humans. A collaborative study is conducted in which 108 samples from the three species are analyzed in seven independent laboratories. This study demonstrates that the TNA is a panspecies assay that can be performed in several different laboratories with a high degree of quantitative agreement and precision
diagnostics
-
the development, performance characteristics and validation using human serum of a robust and rugged format of the LTx neutralization activity (TNA) assay is reported and its application in evaluating immune serum from humans, Rhesus macaques and rabbits. This format uses standardized and characterized reagents in conjunction with customized interpretive software and a novel mathematical algorithm to calculate and extrapolate multiple reportable values, in addition to ED50, with high specificity, analytical sensitivity, accuracy and precision. This LTx neutralization activity (TNA) assay format is proposed as a unifying platform technology
medicine
-
inducing strong mucosal and systemic immune responses against both anthrax toxins and bacilli after nasal immunization using a synthetic double-stranded RNA (dsRNA), polyriboinosinic-polyribocytidylic acid as adjuvant. The capsular poly-gamma-D-glutamic acid (PGA) from bacillus is immunogenic when conjugated to a carrier protein and dosed intranasally to mice. The nasal immunization with the poly-gamma-D-glutamic acid-carrier protein conjugate in combination with the anthrax protective antigen (PA) protein induces both anti-PGA and anti-PA immune responses in mouse sera and lung mucosal secretions. The anti-PA antibody response is shown to have anthrax lethal toxin neutralization activity. The anti-PGA Abs induced are able to activate complement and kill PGA-producing bacteria. It is feasible to develop a novel dual-action nasal anthrax vaccine
medicine
-
mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge
medicine
-
sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival
medicine
-
engineered lethal anthrax toxin prevents tumor growth by inhibiting angiogenesis (10 nmol/l engineered protective antigen + 5.5 nmol/l lethal factor)
medicine
-
the use of drugs capable of inhibiting Rho GTPase activity, such as statins, may provide a means to attenuate intoxication during Bacillus anthracis infection
medicine
-
anthrax toxin entry and activity differs among immune cells. Macrophages, dendritic cells, and B cells display higher activity of a of fusion protein of the anthrax toxin lethal factor N-terminal domain LFn, residues 1-254, with beta-lactamase, i.e. LFnBLA, than CD4+ and CD8+ T cells in both spleen cell suspension and the purified samples of individual cell types. Expression of anthrax toxin receptor CMG2 is higher in CD4+ and CD8+ T cells, which is not correlated to the intracellular LFnBLA activity
medicine
-
neuronal nitric oxide synthase deficiency in mice causes strikingly increased sensitivity to anthrax lethal toxin, while deficiencies in NOS enzymes iNOS and eNOS have no effect on anthrax lethal toxin-mediated mortality. The increased sensitivity of nNOS2/2 mice is independent of macrophage sensitivity to toxin, or cytokine responses, and can be replicated in nNOS-sufficient wild-type mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Anthrax lethal toxin induces architectural changes in heart morphology of nNOS2/2 mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. Anthrax lethal toxin-treated wild-type mice have no histopathology observed at the light microscopy level. Electron microscopic analyses reveal striking pathological changes in the hearts of both nNOS2/2 and wild-type mice, varying only in severity and timing. Endothelial andcapillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae are observed in both anthrax lethal toxin-treated wild-type and nNOS2/2 mice. Biomarkers of cardiac injury, myoglobin, cardiac troponin-I, and heart fatty acid binding protein, are elevated in anthrax lethal toxin-treated mice very rapidly and reach concentrations rarely reported in mice. The potent nitric oxide scavenger, 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide, i.e. carboxy-PTIO, shows some protective effect against anthrax lethal toxin
medicine
-
anthrax lethal factor is a specific biomarker of active infection by Bacillus anthracis
medicine
-
blood borne lethal toxin is a novel therapeutic target for combating anthrax
molecular biology
-
anthrax lethal toxin treatment of neutrophils disrupts signaling to downstream MAPK targets in response to TLR stimulation. Following anthrax lethal toxin treatment, ERK family and p38 phosphorylation are nearly completely blocked, but signaling to JNK family members persists in vitro and ex vivo. In contrast to previous reports involving human neutrophils, anthrax lethal toxin treatment of murine neutrophils increases their production of superoxide in response to PMA or TLR stimulation in vitro or ex vivo. Although this enhanced superoxide production correlates with effects due to the lethal toxin-induced blockade of ERK signaling, it requires JNK signaling that remains largely intact despite the activity of anthrax lethal toxin
molecular biology
-
Bacillus anthracis represses the immune response, in part by altering chromatin accessibility of IL-8 promoter to NFkappaB in epithelial cells. This epigenetic reprogramming, in addition to previously reported effects of lethal toxin, represents an efficient strategy used by Bacillus anthracis for invading the host
molecular biology
-
celastrol is identified as an inhibitor of lethal toxin-mediated macrophage lysis and suggests an inhibitory mechanism involving inhibition of the proteasome pathway
molecular biology
-
it is shown that treatment of RAW 264.7 murine macrophage cells with anthrax lethaltoxin induces autophagy suggesting a protective role as autophagy inhibition using 3-methyladenine results in an accelerated cell death
molecular biology
-
lethal toxin triggers the formation of a membrane-associated inflammasome complex in murine macrophages consisting of caspase-1 and Nalp1b, resulting in cleavage of cytosolic caspase-1 substrates and cell death
molecular biology
-
microarray analysis is used to investigate the effects of Bacillus anthracis lethal toxin on human neutrophil-like NB-4 cells to identify markers of intoxication. Genes down-regulated after a 2 h lethal toxin exposure include those encoding chemokines and transcription factors. Significant decreases in the mRNA of interleukin-8, CCL20, CCL3 and CCL4 are observed using real-time PCR. The decreases are more pronounced at 4 and 8 h and are lethal toxin-specific. Decreases in chemokine protein levels are evident after 24 h and are sensitive to low concentrations of lethal toxin. Co-incubation with an anti-lethal factor mAb restores levels of interleukin-8 to 100% and 50%, respectively
molecular biology
-
primary keratinocytes are resistant to LeTx cytotoxicity, and MEK cleavage does not correlate with LeTx cytotoxicity. LeTx is considered as an anti-inflammatory agent, however it upregulates RANTES
molecular biology
-
proteasome inhibitors block anthrax lethal toxin-mediated caspase-1 activation and can protect against cell death, indicating that the degradation of at least one cellular protein is required for cell death. Proteins can be degraded by the proteasome via the N-end rule. Using amino acid derivatives that act as inhibitors of this pathway, it is shown that the N-end rule is required for anthrax lethal toxin-mediated caspase-1 activation and cell death. The Streptomyces olivoreti peptide bestatin, which inhibits leucine, alanine and arginine aminopeptidases, protects macrophages against anthrax lethal toxin. c-IAP1, a mammalian member of the inhibitor of apoptosis protein (IAP) family is identified, as a novel N-end rule substrate degraded in macrophages treated with anthrax lethal toxin
molecular biology
-
protein expression profile of murine macrophages RAW264.7 treated with LeTx is analyzed using two-dimensional polyacrylamide gel electrophoresis and MALDI-TOF MS. Among the differentially expressed spots, cleaved mitogen-activated protein kinase kinase 1 acting as a negative element in the signal transduction pathway, and glucose-6-phosphate dehydrogenase playing a role in the protection of cells from hyperproduction of active oxygen are up-regulated LeTx-treated macrophages
molecular biology
-
results suggest that this toxin delivery system is capable of stimulating protective immune responses where effective immunization requires stimulation of both classes of T cells
molecular biology
-
the cellular damage inflicted by anthrax lethal toxin depends not only on the innate responses but also on the maturation stage of the cell, which modulates the more general caspase-1-independent responses
molecular biology
-
the effects of lethal toxin on the transcriptional regulation of the VCAM1 gene, which contains binding sites in its promoter region for NF-kappaB, IFN regulatory factor-1 (IRF-1), Sp1, GATA-2, and AP-1, in primary human endothelial cells is examined. Lethal toxin enhances cytokine-induced activation of NF-kappaB and IRF-1 which are key factors in the lethal toxin-mediated enhancement of TNF-induced VCAM-1 expression. Altering the activity of key transcription factors involved in host response to infection may be a critical mechanism by which lethal toxin contributes to anthrax pathogenesis
molecular biology
-
the in vitro effects of thermal stress on the killing of murine macrophages by anthrax lethal toxin are investigated. Heat shock rapidly halts anthrax lethal toxin-induced cell death without any impact on toxin uptake or mitogen-activated protein kinases cleavage, by a mechanism independent of novel protein synthesis, p38 activation, HSP90 activity or proteasome inhibition. Rather, heat shock prevents the activation of procaspase-1 in anthrax lethal toxin -treated cells, apparently by the sequestration of pro-caspase-1 in a large, inhibitory complex. Heat-shocked cell lysates strongly inhibit the active caspase-1 heterotetramer in vitro, independent of a specific inflammasome platform. Results suggest the presence of a cellular, heat shock-inducible, caspase-1 inhibiting factor
molecular biology
-
toxin effects of lethal toxin and edema toxin of Bacillus anthracis in bone marrow dendritic cells stimulated with either LPS or Legionella pneumophila are analysed. Lethal toxin, not ET, is more toxic for cells from BALB/c mice than from C57BL/6 as measured by 7-AAD uptake. Results support the conclusion that lethal toxin and edema toxin are not uniformly suppressive of dendritic cell function but rather modulate function up or down depending on variables such as the function tested, the microbial stimulus used, and the genetic variation in innate immune response mechanisms in the host cell
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vitale, G.; Bernardi, L.; Napolitani, G.; Mock, M.; Montecucco, C.
Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor
Biochem. J.
352
739-745
2000
Bacillus anthracis
Duesbery, N.S.; Webb, C.P.; Leppla, S.H.; Gordon, V.M.; Klimpel, K.R.; Copeland, T.D.; Ahn, N.G.; Oskarsson, M.K.; Fukasawa, K.; Paull, K.D.; Vande Woude, G.F.
Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor
Science
280
734-737
1998
Bacillus anthracis
Pannifer, A.D.; Wong, T.Y.; Schwarzenbacher, R.; Renatus, M.; Petosa, C.; Bienkowska, J.; Lacy, D.B.; Collier, R.J.; Park, S.; Leppla, S.H.; Hanna, P.; Liddington, R.C.
Crystal structure of the anthrax lethal factor
Nature
414
229-233
2001
Bacillus anthracis
Tonello, F.; Ascenzi, P.; Montecucco, C.
The metalloproteolytic activity of the anthrax lethal factor is substrate-inhibited
J. Biol. Chem.
278
40075-40078
2003
Bacillus anthracis
Pellizzari, R.; Guidi-Rontani, C.; Vitale, G.; Mock, M.; Montecucco, C.
Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha
FEBS Lett.
462
199-204
1999
Bacillus anthracis
Rossetto, O.; de Bernard, M.; Pellizzari, R.; Vitale, G.; Caccin, P.; Schiavo, G.; Montecucco, C.
Bacterial toxins with intracellular protease activity
Clin. Chim. Acta
291
189-199
2000
Bacillus anthracis
Glomski, I.J.; Fritz, J.H.; Keppler, S.J.; Balloy, V.; Chignard, M.; Mock, M.; Goossens, P.L.
Murine splenocytes produce inflammatory cytokines in MyD88-dependent response to Bacillus anthracis spores
cell. Microbiol.
9
502-513
2007
Bacillus anthracis
Gubbins, M.J.; Berry, J.D.; Corbett, C.R.; Mogridge, J.; Yuan, X.Y.; Schmidt, L.; Nicolas, B.; Kabani, A.; Tsang, R.S.
Production and characterization of neutralizing monoclonal antibodies that recognize an epitope in domain 2 of Bacillus anthracis protective antigen
FEMS Immunol. Med. Microbiol.
47
436-443
2006
Bacillus anthracis
Bergman, N.H.; Passalacqua, K.D.; Gaspard, R.; Shetron-Rama, L.M.; Quackenbush, J.; Hanna, P.C.
Murine macrophage transcriptional responses to Bacillus anthracis infection and intoxication
Infect. Immun.
73
1069-1080
2005
Bacillus anthracis
Comer, J.E.; Galindo, C.L.; Chopra, A.K.; Peterson, J.W.
GeneChip analyses of global transcriptional responses of murine macrophages to the lethal toxin of Bacillus anthracis
Infect. Immun.
73
1879-1885
2005
Bacillus anthracis
Koya, V.; Moayeri, M.; Leppla, S.H.; Daniell, H.
Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge
Infect. Immun.
73
8266-8274
2005
Bacillus anthracis
Xu, L.; Frucht, D.M.
Bacillus anthracis: A multi-faceted role for anthrax lethal toxin in thwarting host immune defenses
Int. J. Biochem. Cell Biol.
39
20-24
2007
Bacillus anthracis
Baillie, L.W.J.
Past, imminent and future human medical countermeasures for anthrax
J. Appl. Microbiol.
101
594-606
2006
Bacillus anthracis
Cui, X.; Li, Y.; Li, X.; Haley, M.; Moayeri, M.; Fitz, Y.; Leppla, S.H.; Eichacker, P.Q.
Sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival
J. Infect. Dis.
193
829-840
2006
Bacillus anthracis
Gujraty, K.; Sadacharan, S.; Frost, M.; Poon, V.; kane, R.S.; Mogridge, J.
Functional characterization of peptide-based anthrax toxin inhibitors
Mol. Pharmacol.
2
367-372
2005
Bacillus anthracis
-
Mendelson, I.; Gat, O.; Aloni-Grinstein, R.; Altboum, Z.; Inbar, I.; Kronman, C.; Bar-Haim, E.; Cohen, S.; Velan, B.; Shafferman, A.
Efficacious, nontoxigenic Bacillus anthracis spore vaccines based on strains expressing mutant variants of lethal toxin components
Vaccine
23
5688-5697
2005
Bacillus anthracis
Sloat, B.R.; Cui, Z.
Nasal immunozation with a dual antigen anthrax vaccine induced strong mucosal and systemic immune responses against toxins and bacilli
Vaccine
24
6405-6413
2006
Bacillus anthracis
Moayeri, M.; Robinson, T.M.; Leppla, S.H.; Karginov, V.A.
In vivo efficacy of beta-cyclodextrin derivatives against anthrax lethal toxin
Antimicrob. Agents Chemother.
52
2239-2241
2008
Bacillus anthracis
Chvyrkova, I.; Zhang, X.C.; Terzyan, S.
Lethal factor of anthrax toxin binds monomeric form of protective antigen
Biochem. Biophys. Res. Commun.
360
690-695
2007
Bacillus anthracis (Q52NH3), Bacillus anthracis
Karginov, V.A.; Nestorovich, E.M.; Schmidtmann, F.; Robinson, T.M.; Yohannes, A.; Fahmi, N.E.; Bezrukov, S.M.; Hecht, S.M.
Inhibition of S. aureus alpha-hemolysin and B. anthracis lethal toxin by beta-cyclodextrin derivatives
Bioorg. Med. Chem.
15
5424-5431
2007
Bacillus anthracis
Gaddis, B.D.; Avramova, L.V.; Chmielewski, J.
Inhibitors of anthrax lethal factor
Bioorg. Med. Chem. Lett.
17
4575-4578
2007
Bacillus anthracis
Muehlbauer, S.M.; Evering, T.H.; Bonuccelli, G.; Squires, R.C.; Ashton, A.W.; Porcelli, S.A.; Lisanti, M.P.; Brojatsch, J.
Anthrax lethal toxin kills macrophages in a strain-specific manner by apoptosis or caspase-1-mediated necrosis
Cell Cycle
6
758-766
2007
Bacillus anthracis
Wickliffe, K.E.; Leppla, S.H.; Moayeri, M.
Anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome
Cell. Microbiol.
10
332-343
2008
Bacillus anthracis
Rossi Paccani, S.; Tonello, F.; Patrussi, L.; Capitani, N.; Simonato, M.; Montecucco, C.; Baldari, C.T.
Anthrax toxins inhibit immune cell chemotaxis by perturbing chemokine receptor signalling
Cell. Microbiol.
9
924-929
2007
Bacillus anthracis
During, R.L.; Gibson, B.G.; Li, W.; Bishai, E.A.; Sidhu, G.S.; Landry, J.; Southwick, F.S.
Anthrax lethal toxin paralyzes actin-based motility by blocking Hsp27 phosphorylation
EMBO J.
26
2240-2250
2007
Bacillus anthracis
Kuzmic, P.; Cregar, L.; Millis, S.Z.; Goldman, M.
Mixed-type noncompetitive inhibition of anthrax lethal factor protease by aminoglycosides
FEBS J.
273
3054-3062
2006
Bacillus anthracis
Juris, S.J.; Melnyk, R.A.; Bolcome, R.E.; Chan, J.; Collier, R.J.
Cross-linked forms of the isolated N-terminal domain of the lethal factor are potent inhibitors of anthrax toxin
Infect. Immun.
75
5052-5058
2007
Bacillus anthracis
Liu, S.; Wang, H.; Currie, B.M.; Molinolo, A.; Leung, H.J.; Moayeri, M.; Basile, J.R.; Alfano, R.W.; Gutkind, J.S.; Frankel, A.E.; Bugge, T.H.; Leppla, S.H.
Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature
J. Biol. Chem.
283
529-540
2008
Bacillus anthracis
Chang, H.H.; Tsai, M.F.; Chung, C.P.; Chen, P.K.; Hu, H.I.; Kau, J.H.; Huang, H.H.; Lin, H.C.; Sun, D.S.
Single-step purification of recombinant anthrax lethal factor from periplasm of Escherichia coli
J. Biotechnol.
126
277-285
2006
Bacillus anthracis
Schepetkin, I.A.; Khlebnikov, A.I.; Kirpotina, L.N.; Quinn, M.T.
Novel small-molecule inhibitors of anthrax lethal factor identified by high-throughput screening
J. Med. Chem.
49
5232-5244
2006
Bacillus anthracis
Dalkas, G.A.; Papakyriakou, A.; Vlamis-Gardikas, A.; Spyroulias, G.A.
Low molecular weight inhibitors of the protease anthrax lethal factor
Mini Rev. Med. Chem.
8
290-306
2008
Bacillus anthracis
Alfano, R.W.; Leppla, S.H.; Liu, S.; Bugge, T.H.; Herlyn, M.; Smalley, K.S.; Bromberg-White, J.L.; Duesbery, N.S.; Frankel, A.E.
Cytotoxicity of the matrix metalloproteinase-activated anthrax lethal toxin is dependent on gelatinase expression and B-RAF status in human melanoma cells
Mol. Cancer Ther.
7
1218-1226
2008
Bacillus anthracis
Guichard, A.; Park, J.M.; Cruz-Moreno, B.; Karin, M.; Bier, E.
Anthrax lethal factor and edema factor act on conserved targets in Drosophila
Proc. Natl. Acad. Sci. USA
103
3244-3249
2006
Bacillus anthracis
Bolcome, R.E.; Sullivan, S.E.; Zeller, R.; Barker, A.P.; Collier, R.J.; Chan, J.
Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature
Proc. Natl. Acad. Sci. USA
105
2439-2444
2008
Bacillus anthracis
Fink, S.L.; Bergsbaken, T.; Cookson, B.T.
Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms
Proc. Natl. Acad. Sci. USA
105
4312-4317
2008
Bacillus anthracis
Barson, H.V.; Mollenkopf, H.; Kaufmann, S.H.; Rijpkema, S.
Anthrax lethal toxin suppresses chemokine production in human neutrophil NB-4 cells
Biochem. Biophys. Res. Commun.
374
288-293
2008
Bacillus anthracis
Tan, Y.K.; Kusuma, C.M.; St John, L.J.; Vu, H.A.; Alibek, K.; Wu, A.
Induction of autophagy by anthrax lethal toxin
Biochem. Biophys. Res. Commun.
379
293-297
2009
Bacillus anthracis
Jung, K.H.; Seo, G.M.; Yoon, J.W.; Park, K.S.; Kim, J.C.; Kim, S.J.; Oh, K.G.; Lee, J.H.; Chai, Y.G.
Protein expression pattern of murine macrophages treated with anthrax lethal toxin
Biochim. Biophys. Acta
1784
1501-1506
2008
Bacillus anthracis
Gaddis, B.D.; Rubert Perez, C.M.; Chmielewski, J.
Inhibitors of anthrax lethal factor based upon N-oleoyldopamine
Bioorg. Med. Chem. Lett.
18
2467-2470
2008
Bacillus anthracis
Reig, N.; Jiang, A.; Couture, R.; Sutterwala, F.S.; Ogura, Y.; Flavell, R.A.; Mellman, I.; van der Goot, F.G.
Maturation modulates caspase-1-independent responses of dendritic cells to Anthrax lethal toxin
Cell. Microbiol.
10
1190-1207
2008
Bacillus anthracis
Wickliffe, K.E.; Leppla, S.H.; Moayeri, M.
Killing of macrophages by anthrax lethal toxin: involvement of the N-end rule pathway
Cell. Microbiol.
10
1352-1362
2008
Bacillus anthracis
Levin, T.C.; Wickliffe, K.E.; Leppla, S.H.; Moayeri, M.
Heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin
Cell. Microbiol.
10
2434-2446
2008
Bacillus anthracis
Omland, K.S.; Brys, A.; Lansky, D.; Clement, K.; Lynn, F.; Lynn, F.
Interlaboratory comparison of results of an anthrax lethal toxin neutralization assay for assessment of functional antibodies in multiple species
Clin. Vaccine Immunol.
15
946-953
2008
Bacillus anthracis
Chou, P.J.; Newton, C.A.; Perkins, I.; Friedman, H.; Klein, T.W.
Suppression of dendritic cell activation by anthrax lethal toxin and edema toxin depends on multiple factors including cell source, stimulus used, and function tested
DNA Cell Biol.
27
637-648
2008
Bacillus anthracis
Shaw, C.A.; Starnbach, M.N.
Both CD4+ and CD8+ T cells respond to antigens fused to anthrax lethal toxin
Infect. Immun.
76
2603-2611
2008
Bacillus anthracis
Nour, A.M.; Yeung, Y.G.; Santambrogio, L.; Boyden, E.D.; Stanley, E.R.; Brojatsch, J.
Anthrax lethal toxin triggers the formation of a membrane-associated inflammasome complex in murine macrophages
Infect. Immun.
77
1262-1271
2009
Bacillus anthracis
deCathelineau, A.M.; Bokoch, G.M.
Inactivation of rho GTPases by statins attenuates anthrax lethal toxin activity
Infect. Immun.
77
348-359
2009
Bacillus anthracis
Kocer, S.S.; Matic, M.; Ingrassia, M.; Walker, S.G.; Roemer, E.; Licul, G.; Simon, S.R.
Effects of anthrax lethal toxin on human primary keratinocytes
J. Appl. Microbiol.
105
1756-1767
2008
Bacillus anthracis
Xu, L.; Fang, H.; Frucht, D.M.
Anthrax lethal toxin increases superoxide production in murine neutrophils via differential effects on MAPK signaling pathways
J. Immunol.
180
4139-4147
2008
Bacillus anthracis
Warfel, J.M.; DAgnillo, F.
Anthrax lethal toxin enhances TNF-induced endothelial VCAM-1 expression via an IFN regulatory factor-1-dependent mechanism
J. Immunol.
180
7516-7524
2008
Bacillus anthracis
Alfano, R.W.; Leppla, S.H.; Liu, S.; Bugge, T.H.; Meininger, C.J.; Lairmore, T.C.; Mulne, A.F.; Davis, S.H.; Duesbery, N.S.; Frankel, A.E.
Matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis
Mol. Cancer Res.
7
452-461
2009
Bacillus anthracis
Chapelsky, S.; Batty, S.; Frost, M.; Mogridge, J.
Inhibition of anthrax lethal toxin-induced cytolysis of RAW264.7 cells by celastrol
PLoS ONE
3
e1421
2008
Bacillus anthracis
Raymond, B.; Batsche, E.; Boutillon, F.; Wu, Y.Z.; Leduc, D.; Balloy, V.; Raoust, E.; Muchardt, C.; Goossens, P.L.; Touqui, L.
Anthrax lethal toxin impairs IL-8 expression in epithelial cells through inhibition of histone H3 modification
PLoS Pathog.
5
e1000359
2009
Bacillus anthracis
Ha, S.D.; Ham, B.; Mogridge, J.; Saftig, P.; Lin, S.; Kim, S.O.
Cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2-mediated delivery of anthrax lethal factor into the cytoplasm
J. Biol. Chem.
285
2120-2129
2010
Bacillus anthracis
Pentelute, B.L.; Barker, A.P.; Janowiak, B.E.; Kent, S.B.; Collier, R.J.
A semisynthesis platform for investigating structure-function relationships in the N-terminal domain of the anthrax Lethal Factor
ACS Chem. Biol.
5
359-364
2010
Bacillus anthracis
Raymond, B.; Ravaux, L.; Memet, S.; Wu, Y.; Sturny-Leclere, A.; Leduc, D.; Denoyelle, C.; Goossens, P.L.; Paya, M.; Raymondjean, M.; Touqui, L.
Anthrax lethal toxin down-regulates type-IIA secreted phospholipase A(2) expression through MAPK/NF-kappaB inactivation
Biochem. Pharmacol.
79
1149-1155
2010
Bacillus anthracis
Ngai, S.; Batty, S.; Liao, K.C.; Mogridge, J.
An anthrax lethal factor mutant that is defective at causing pyroptosis retains proapoptotic activity
FEBS J.
277
119-127
2010
Bacillus anthracis
Kong, Y.; Guo, Q.; Yu, C.; Dong, D.; Zhao, J.; Cai, C.; Hou, L.; Song, X.; Fu, L.; Xu, J.; Chen, W.
Fusion protein of DELTA 27LFn and EFn has the potential as a novel anthrax toxin inhibitor
FEBS Lett.
583
1257-1260
2009
Bacillus anthracis
Zakharova, M.Y.; Kuznetsov, N.A.; Dubiley, S.A.; Kozyr, A.V.; Fedorova, O.S.; Chudakov, D.M.; Knorre, D.G.; Shemyakin, I.G.; Gabibov, A.G.; Kolesnikov, A.V.
Substrate recognition of anthrax lethal factor examined by combinatorial and pre-steady-state kinetic approaches
J. Biol. Chem.
284
17902-17913
2009
Bacillus anthracis
Chiu, T.L.; Solberg, J.; Patil, S.; Geders, T.W.; Zhang, X.; Rangarajan, S.; Francis, R.; Finzel, B.C.; Walters, M.A.; Hook, D.J.; Amin, E.A.
Identification of novel non-hydroxamate anthrax toxin lethal factor inhibitors by topomeric searching, docking and scoring, and in vitro screening
J. Chem. Inf. Model.
49
2726-2734
2009
Bacillus anthracis
Hu, H.; Leppla, S.H.
Anthrax toxin uptake by primary immune cells as determined with a lethal factor-beta-lactamase fusion protein
PLoS ONE
4
e7946
2009
Bacillus anthracis
Moayeri, M.; Crown, D.; Dorward, D.W.; Gardner, D.; Ward, J.M.; Li, Y.; Cui, X.; Eichacker, P.; Leppla, S.H.
The heart is an early target of anthrax lethal toxin in mice: a protective role for neuronal nitric oxide synthase (nNOS)
PLoS Pathog.
5
e1000456
2009
Bacillus anthracis
Abrami, L.; Kunz, B.; van der Goot, F.G.
Anthrax toxin triggers the activation of src-like kinases to mediate its own uptake
Proc. Natl. Acad. Sci. USA
107
1420-1424
2010
Bacillus anthracis
Dalkas, G.A.; Papakyriakou, A.; Vlamis-Gardikas, A.; Spyroulias, G.A.
Insights into the anthrax lethal factor-substrate interaction and selectivity using docking and molecular dynamics simulations
Protein Sci.
18
1774-1785
2009
Bacillus anthracis
Kuklenyik, Z.; Boyer, A.E.; Lins, R.; Quinn, C.P.; Gallegos-Candela, M.; Woolfitt, A.; Pirkle, J.L.; Barr, J.R.
Comparison of MALDI-TOF-MS and HPLC-ESI-MS/MS for endopeptidase activity-based quantification of anthrax lethal factor in serum
Anal. Chem.
83
1760-1765
2011
Bacillus anthracis
Li, F.; Terzyan, S.; Tang, J.
Subsite specificity of anthrax lethal factor and its implications for inhibitor development
Biochem. Biophys. Res. Commun.
407
400-405
2011
Bacillus anthracis
Saebel, C.E.; Carbone, R.; Dabous, J.R.; Lo, S.Y.; Siemann, S.
Preparation and characterization of cobalt-substituted anthrax lethal factor
Biochem. Biophys. Res. Commun.
416
106-110
2011
Bacillus anthracis
Dalkas, G.A.; Chasapis, C.T.; Gkazonis, P.V.; Bentrop, D.; Spyroulias, G.A.
Conformational dynamics of the anthrax lethal factor catalytic center
Biochemistry
49
10767-10769
2010
Bacillus anthracis (P15917)
Little, S.F.; Webster, W.M.; Fisher, D.E.
Monoclonal antibodies directed against protective antigen of Bacillus anthracis enhance lethal toxin activity in vivo
FEMS Immunol. Med. Microbiol.
62
11-22
2011
Bacillus anthracis, Bacillus anthracis BH450
Liu, T.; Milia, E.; Warburton, R.R.; Hill, N.S.; Gaestel, M.; Kayyali, U.S.
Anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling
J. Cell. Physiol.
227
1438-1445
2012
Bacillus anthracis
Thomas, J.; Epshtein, Y.; Chopra, A.; Ordog, B.; Ghassemi, M.; Christman, J.W.; Nattel, S.; Cook, J.L.; Levitan, I.
Anthrax lethal factor activates K+ channels to induce IL-1beta secretion in macrophages
J. Immunol.
186
5236-5243
2011
Bacillus anthracis
Vuyisich, M.; Sanders, C.; Graves, S.
Binding and cell intoxication studies of anthrax lethal toxin
Mol. Biol. Rep.
2012
1-7
2012
Bacillus anthracis
Guichard, A.; McGillivray, S.; Cruz-Moreno, B.; Van Sorge, N.; Nizet, V.; Bier, E.
Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst
Nature
467
854-858
2010
Bacillus anthracis
Rivera, J.; Cordero, R.; Nakouzi, A.; Frases, S.; Nicola, A.; Casadevall, A.
Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins
Proc. Natl. Acad. Sci. USA
107
19002-19007
2010
Bacillus anthracis, Bacillus anthracis 34F2
Bromberg-White, J.; Lee, C.S.; Duesbery, N.
Consequences and utility of the zinc-dependent metalloprotease activity of anthrax lethal toxin
Toxins
2
1038-1053
2010
Bacillus anthracis
Xie, T.; Auth, R.D.; Frucht, D.M.
The effects of anthrax lethal toxin on host barrier function
Toxins
3
591-607
2011
Bacillus anthracis
Maize, K.; Kurbanov, E.; De La Mora-Rey, T.; Geders, T.; Hwang, D.; Walters, M.; Johnson, R.; Amin, E.; Finzel, B.
Anthrax toxin lethal factor domain 3 is highly mobile and responsive to ligand binding
Acta Crystallogr. Sect. D
70
2813-2822
2014
Bacillus anthracis (P15917)
Moayeri, M.; Crown, D.; Jiao, G.; Kim, S.; Johnson, A.; Leysath, C.; Leppla, S.
Small-molecule inhibitors of lethal factor protease activity protect against anthrax infection
Antimicrob. Agents Chemother.
57
4139-4145
2013
Bacillus anthracis (P15917), Bacillus anthracis
Vourtsis, D.; Chasapis, C.; Pairas, G.; Bentrop, D.; Spyroulias, G.
NMR conformational properties of an Anthrax lethal factor domain studied by multiple amino acid-selective labeling
Biochem. Biophys. Res. Commun.
450
335-340
2014
Bacillus anthracis (P15917)
Montpellier, L.; Siemann, S.
Effect of pH on the catalytic function and zinc content of native and immobilized anthrax lethal factor
FEBS Lett.
587
317-321
2013
Bacillus anthracis (P15917)
Ouyang, W.; Torigoe, C.; Fang, H.; Xie, T.; Frucht, D.
Anthrax lethal toxin inhibits translation of hypoxia-inducible factor 1alpha and causes decreased tolerance to hypoxic stress
J. Biol. Chem.
289
4180-4190
2014
Bacillus anthracis
Antonelli, A.; Zhang, Y.; Golub, L.; Johnson, F.; Simon, S.
Inhibition of anthrax lethal factor by curcumin and chemically modified curcumin derivatives
J. Enzyme Inhib. Med. Chem.
29
663-669
2014
Bacillus anthracis
Lo, S.; Sbel, C.; Webb, M.; Walsby, C.; Siemann, S.
High metal substitution tolerance of anthrax lethal factor and characterization of its active copper-substituted analogue
J. Inorg. Biochem.
140
12-22
2014
Bacillus anthracis (P15917)
Liao, H.; Liu, H.; Chen, W.; Ho, Y.
Structure-based pharmacophore modeling and virtual screening to identify novel inhibitors for anthrax lethal factor
Med. Chem. Res.
23
3725-3732
2014
Bacillus anthracis (P15917)
-
Sun, C.; Fang, H.; Xie, T.; Auth, R.; Patel, N.; Murray, P.; Snoy, P.; Frucht, D.
Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria
PLoS ONE
7
e33583
2012
Bacillus anthracis (P15917), Bacillus anthracis
Levinsohn, J.; Newman, Z.; Hellmich, K.; Fattah, R.; Getz, M.; Liu, S.; Sastalla, I.; Leppla, S.; Moayeri, M.
Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome
PLoS Pathog.
8
e1002638
2012
Bacillus anthracis (P15917)
Kassab, E.; Darwish, M.; Timsah, Z.; Liu, S.; Leppla, S.; Frankel, A.; Abi-Habib, R.
Cytotoxicity of anthrax lethal toxin to human acute myeloid leukemia cells is nonapoptotic and dependent on extracellular signal-regulated kinase 1/2 activity
Transl. Oncol.
6
25-32
2013
Bacillus anthracis (P15917)
Lo, S.Y.; Saebel, C.E.; Mapletoft, J.P.J.; Siemann, S.
Influence of chemical denaturants on the activity, fold and zinc status of anthrax lethal factor
Biochem. Biophys. Rep.
1
68-77
2015
Bacillus anthracis (P15917)
Goldberg, A.B.; Turk, B.E.
Inhibitors of the metalloproteinase anthrax lethal factor
Curr. Top. Med. Chem.
16
2350-2358
2016
Bacillus anthracis (P15917), Bacillus anthracis
Maize, K.M.; Kurbanov, E.K.; Johnson, R.L.; Amin, E.A.; Finzel, B.C.
Ligand-induced expansion of the S1 site in the anthrax toxin lethal factor
FEBS Lett.
589
3836-3841
2015
Bacillus anthracis (P15917), Bacillus anthracis
Zhang, W.W.; Wang, X.; Xie, P.; Yuan, S.T.; Liu, Q.H.
Anthrax lethal toxin suppresses high glucose induced VEGF over secretion through a post-translational mechanism
Int. J. Ophthalmol.
8
453-458
2015
Bacillus anthracis (P15917)
Ma, P.; Cardenas, A.E.; Chaudhari, M.I.; Elber, R.; Rempe, S.B.
The impact of protonation on early translocation of anthrax lethal factor kinetics from molecular dynamics simulations and milestoning theory
J. Am. Chem. Soc.
139
14837-14840
2017
Bacillus anthracis (P15917)
Ouyang, W.; Guo, P.; Fang, H.; Frucht, D.M.
Anthrax lethal toxin rapidly reduces c-Jun levels by inhibiting c-Jun gene transcription and promoting c-Jun protein degradation
J. Biol. Chem.
292
17919-17927
2017
Bacillus anthracis (P15917), Bacillus anthracis
Goldberg, A.B.; Cho, E.; Miller, C.J.; Lou, H.J.; Turk, B.E.
Identification of a substrate-selective exosite within the metalloproteinase anthrax lethal factor
J. Biol. Chem.
292
814-825
2017
Bacillus anthracis (P15917), Bacillus anthracis
Krantz, B.
Anthrax lethal toxin co-complexes are stabilized by contacts between adjacent lethal factors
J. Gen. Physiol.
148
1966-1970
2016
Bacillus anthracis (P15917)
Young, C.J.; Richard, K.; Beruar, A.; Lo, S.Y.; Siemann, S.
An investigation of the pH dependence of copper-substituted anthrax lethal factor and its mechanistic implications
J. Inorg. Biochem.
182
1-8
2018
Bacillus anthracis (P15917)
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