3.4.24.69: bontoxilysin
This is an abbreviated version!
For detailed information about bontoxilysin, go to the full flat file.
Reaction
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates
=
Synonyms
abobotulinumtoxinA, antigen E, Balc424, BoNT, BoNT A, BoNT B, BoNT E, BoNT F, BoNT F/A, BoNT LC, BoNT LC/A, BoNT serotype A, BoNT serotype E, BoNT serotype F, BoNT-A, BoNT-C, BoNT-D, BoNT-E, BoNT-F, BoNT/A, BoNT/A LC, BoNT/A Lc endopeptidase, BoNT/A-LC, BoNT/A1, BoNT/A2, BoNT/A3, BoNT/A4, BoNT/A5, BoNT/A6, BoNT/A8, BoNT/B, BoNT/B light chain protease, BoNT/B-LC, BoNT/B1, BoNT/B6, BoNT/C, BoNT/C1, BoNT/C1-LC, BoNT/C3, BoNT/CD, BoNT/D, BoNT/E, BoNT/F, BoNT/F proteolytic F toxin, BoNT/F-LC, BoNT/F1, BoNT/F5, BoNT/F6, BoNT/F7, BoNT/F9, BoNT/FA, BoNT/G, BoNT/HA, BoNT/T, BoNT/X, BoNTA, BoNTA endopeptidase, BoNTB, BoNTC, BoNTE, BoNTF, Bontoxilysin C1, botox A, botulinum A neurotoxin light chain, Botulinum neurotoxin, botulinum neurotoxin a, botulinum neurotoxin A light chain, botulinum neurotoxin A protease, botulinum neurotoxin A subtype 1, botulinum neurotoxin A subtype 2, botulinum neurotoxin A subtype 6, botulinum neurotoxin A3, botulinum neurotoxin A4, botulinum neurotoxin A8 subtype, botulinum neurotoxin B, botulinum neurotoxin B protease, botulinum neurotoxin C, botulinum neurotoxin D light chain, botulinum neurotoxin E, botulinum neurotoxin endopeptidase, botulinum neurotoxin F, botulinum neurotoxin serotype A, botulinum neurotoxin serotype A endopeptidase, botulinum neurotoxin serotype A light chain, botulinum neurotoxin serotype A protease, botulinum neurotoxin serotype B, botulinum neurotoxin serotype BA, botulinum neurotoxin serotype C1, botulinum neurotoxin serotype C1 light chain protease, botulinum neurotoxin serotype D, botulinum neurotoxin serotype E, botulinum neurotoxin serotype F, botulinum neurotoxin serotype FA, botulinum neurotoxin serotype G, botulinum neurotoxin serotype H, botulinum neurotoxin subtype A, botulinum neurotoxin subtype A3, botulinum neurotoxin subtype A4, botulinum neurotoxin subtype B6, botulinum neurotoxin subtype F5, botulinum neurotoxin type A, botulinum neurotoxin type A light chain, botulinum neurotoxin type B, botulinum neurotoxin type C, botulinum neurotoxin type D, botulinum neurotoxin type E, botulinum neurotoxin type F, botulinum neurotoxin type F light chain, botulinum neurotoxin type G, botulinum neurotoxin type HA, botulinum neurotoxin X, Botulinum neurotoxin-A, botulinum toxin, botulinum toxin C3, botulinum toxin serotype E, botulinum toxin serotype F, botulinum toxin type A, botulinum toxin type B, botulinum toxin type F, Botulinumtoxin A, BoTxA, C2 toxin, CDC69016, Clostridium botulinum A2 neurotoxin, Clostridium botulinum C2 toxin, Clostridium botulinum neurotoxin, Clostridium botulinum neurotoxin A1, Clostridium botulinum neurotoxin F, Clostridium botulinum neurotoxin serotype A, Clostridium botulinum neurotoxin serotype A light chain, Clostridium botulinum neurotoxin type E, Clostridium botulinum serotype D neurotoxin, CNT endopeptidase, D-4947 L-TC, daxibotulinumtoxinA, HCB, HCE, incobotulinumtoxinA, LC/A, LC/D, LC/F5, LC/HA, LC/X, LCA, LcB, lcc1, LCD, LCE, LCF, LHn/D, More, mosaic toxin, neurotoxin A, NT, onabotulinumtoxinA, serotype D botulinum neurotoxin, subtype A4 neurotoxin, TeNT, Tetanus neurotoxin, type A BoNT, type A botulinum neurotoxin, type A botulinum neurotoxin light chain, type A botulinum neurotoxin protease, type F toxin
ECTree
General Information
General Information on EC 3.4.24.69 - bontoxilysin
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
metabolism
-
the light chain domain of BoNT/A specifically cleaves synaptosome associated protein of 25 kDa, resulting in the inhibition of neurotransmission at the synapse of peripheral neurons
malfunction
-
BoNT acts on the host neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis
malfunction
-
BoNT proteases are blockers of synaptic transmission in host peripheral cholinergic nervous system synapses, they disable host synaptic vesicle exocytosis by cleaving their cytosolic SNARE, i.e. soluble NSF attachment protein receptor, substrates through cleavage by its N-terminal Zn2+-metalloprotease activity, and are the causative agent of botulism and the most poisonous protein known. Presence of BoNT heavy chain in endosomes or the light chain in the cytosol during intoxication may disrupt the host regulatory networks involved in neuronal protein homeostasis and may trigger a stress response comparable to the endoplasmic reticulum unfolded protein response
malfunction
-
BoNT/A injection induces local masseter muscle atrophy in Wistar rats, with alterations of craniofacial bone growth and development, overview
malfunction
-
the endopeptidase activity of light chain domain of BoNT causes inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism in the host
physiological function
-
after entering its target, the neuronal cell, BoNT/B is responsible for synaptobrevin-2, i.e. VAMP2, cleavage. This results in reduced neurotransmitter acetylcholine release from synaptic vesicles, yielding muscular paralysis
physiological function
-
analgesic effect of BoNT/A on neuropathic pain, e.g. chronic refractory neck pain, application on human neck and shoulder muslces
physiological function
-
BoNT/A is a metalloprotease that enters peripheral motor nerve terminals and blocks the release of acetylcholine via the specific cleavage of the synaptosomal-associated protein of 25 kDa. The C-terminus of the heavy chain. HC binds with extraordinary specificity to nerve terminals. Following receptor-mediated endocytosis and acidification of the endosome, the N-terminal portion of the heavy chain, HN, translocates LC across the vesicular membrane into the cytosol. LC acts as Zn2+-dependent endopeptidase to cleave essential protein components of the neurotransmitter release machinery, the SNARE, i.e. soluble N-ethylmaleimide-sensitive factor attachment protein receptor, proteins. This results in disruption of Ca2+-triggered fusion of synaptic vesicles with the plasma membrane. Central effects of BoNT/A and mechanism, detailed overview
physiological function
P10845
BoNT/A is an extremely potent bacterial protein toxin. The Hc fragment of BoNT/A is non-toxic, antigenic, and capable of eliciting a protective immunity in animals challenged with homologous BoNT
physiological function
-
BoNTs are extremely potent neuromuscular poisons that act through soluble N-ethylmaleimide-sensitive factor attachment protein receptor, SNARE, protein cleavage to inhibit neurotransmitter release. Ability of BoNT/A to eliminate localized transmitter and to induce nerve outgrowth.. BoNT/A potently stimulates neuritogenesis at concentrations as low as 0.01 nM in primary cultures enriched with motor neurons isolated from embryonic mouse spinal cord. Presence or absence of SNAP-25 cleavage by BoNT/A is not a determinant factor in BoNT/A-induced neuritogenesis
physiological function
-
BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action
physiological function
-
BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action
physiological function
-
BoNTs inhibit the release of acetylcholine by peripheral cholinergic nerve terminals through a pathway reliant on several distinct stages of action
physiological function
-
botulinum neurotoxins cleave components of the SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor, protein complex, inhibiting acetylcholine release into neuromuscular junctions, resulting in flaccid paralysis and eventual death
physiological function
-
botulinum neurotoxins elicit flaccid paralysis by cleaving SNARE proteins within peripheral neurons. BoNT/A and BoNT/B utilize synaptic vesicle protein 2, SV2, and synaptotagmin, respectively, as receptors for entry into neurons
physiological function
botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation
physiological function
-
Clostridium botulinum neurotoxin is the causative agent of botulism, a neuroparalytic disease
physiological function
-
Clostridium botulinum neurotoxins are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors, SNARE, proteins
physiological function
-
protective potential of the synaptic blocker BoNT/E, that prevents vesicle fusion via the cleavage of the SNARE, i.e. soluble NSF-attachment receptor, protein SNAP-25, i.e. synaptosomal-associated protein of 25 kDa. Acute neuroprotection by the synaptic blocker botulinum neurotoxin E in a Sprague-Dawley adult female rat model of focal cerebral ischemia. BoNT/E inhibits ET-1-induced glutamate release in the hippocampus
physiological function
-
the pharmacologic effect of Botulinumtoxin A includes a reversible blockade of acetylcholine, inhibition of other neurotransmitters, e.g. Substance P and ATP, and the downregulation of axonalexpression of purinergic P2X3- and capsaicin TPRV1-receptors at the nerve endings of the suburothelium, all leading to afferent desensibilization
physiological function
-
Botulinum neurotoxins are produced as progenitor toxin complexes by Clostridium botulinum. The progenitor toxin complexes are composed of enzyme and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver the enzyme through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich progenitor toxin complex on the intestinal lumen preceding its transport across the epithelial barriers
physiological function
P10845
non-toxic non-hemagglutinin protein forms the minimally functional progenitor toxin complex with botulinum neurotoxin which protects the enzyme in the gastrointestinal tract at acidic pH values and releases it upon entry into the circulation
physiological function
-
The botulinum neurotoxin A8 subtype causes severe botulism. The binding characteristics of the botulinum neurotoxin A8 subtype to its main neuronal protein receptor SV2C are unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to subtype BoNT/A1
physiological function
the enzyme inhibit secretion of CGRP neuropeptide neurons
physiological function
the enzyme inhibit secretion of CGRP neuropeptide neurons
physiological function
-
the enzyme inhibit secretion of CGRP neuropeptide neurons
-
physiological function
-
The botulinum neurotoxin A8 subtype causes severe botulism. The binding characteristics of the botulinum neurotoxin A8 subtype to its main neuronal protein receptor SV2C are unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to subtype BoNT/A1
-
physiological function
-
Botulinum neurotoxins are produced as progenitor toxin complexes by Clostridium botulinum. The progenitor toxin complexes are composed of enzyme and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver the enzyme through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich progenitor toxin complex on the intestinal lumen preceding its transport across the epithelial barriers
-
additional information
-
A large toxin complex, L-TC, produced by Clostridium botulinum is composed of neurotoxin BoNT, non-toxic non-hemagglutinin, and hemagglutinin subcomponents, HA-70, -33 and -17
additional information
-
botulinum neurotoxin serotype A causes a life-threatening neuroparalytic disease known as botulism that can afflict large, unprotected populations if the toxin is employed in an act of bioterrorism
additional information
-
polysialylated ganglioside GT1b can act as a potential receptor for BoNT/A, and synthetic glycoconjugates based on GT1b prevent SNAP25 cleavage in spinal cord cells of rat embryos
additional information
-
retrograde transport and transcytosis of catalytically active BoNT/A in cells, mechanisms, overview
additional information
-
The BoNT-receptor complex enters neurons by receptor-mediated endocytosis. Synaptic vesicle protein 2, synaptotagmin I, synaptophysin, vesicle-associated membrane protein 2, and the vacuolar ATPase-proton pump are components of the BoNT-synaptic vesicle protein complex
additional information
-
the catalytic light chain, LC, of botulinum neurotoxin B is unable to enter target neuronal cells by itself. It is brought into the cell, human neuronal SHSY-5Y cells, in association with the BoNT/B heavy chain, HC, through endocytosis
additional information
-
the presence of neurotoxin associated proteins enhances the oral toxicity of the neurotoxin significantly. The whole neurotoxin complex reacts 60 times better with the complex and 35 times better with Hn-33 and NAPs compared to the purified neurotoxin suggesting stronger immunogenicity of neurotoxin associated proteins over that of purified neurotoxin and a higher potential of BoNT/AC and its associated proteins to induce host immune response. BoNT/A in its purified and complex forms induces equal immunogenic response and a 2.5fold higher immunogenic response compared to BoNT/A light and heavy chains
additional information
-
the short synthetic peptide TD-1 can facilitate effective transdermal delivery of BoNT-A through intact skin. Coadministration of TD-1 and BoNT-A to the hindpaw skin of Sprague-Dawley rats results in a significant reduction in plasma extravasation evoked by electrical stimulation, also but less in plasma extravasation evoked by capsaicin. Subcutaneous administration of BoNT-A also reduces vasodilation caused by saphenous nerve stimulation. BoNT-A does not interfere with substance P- and calcitonin gene-related peptide-induced vasodilation
additional information
-
the toxin persists in neuronal cells for an extended period, it maintaines its ability to cleave VAMP2 in human neuronal cells for weeks
additional information
the translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A
additional information
-
the translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A
additional information
-
uptake of BoNT/A, B, E and G into cells requires a dual interaction with gangliosides and the synaptic vesicle proteins synaptotagmin or SV2. Interaction of SV2A, SV2B and SV2C with botulinum neurotoxin F HC, overview
additional information
-
the presence of neurotoxin associated proteins enhances the oral toxicity of the neurotoxin significantly. The whole neurotoxin complex reacts 60 times better with the complex and 35 times better with Hn-33 and NAPs compared to the purified neurotoxin suggesting stronger immunogenicity of neurotoxin associated proteins over that of purified neurotoxin and a higher potential of BoNT/AC and its associated proteins to induce host immune response. BoNT/A in its purified and complex forms induces equal immunogenic response and a 2.5fold higher immunogenic response compared to BoNT/A light and heavy chains
-