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
Other names: botulinum neurotoxin; BoNT
Comments: This zinc enzyme, produced by Clostridium botulinum, occurs as forms A-G that differ in specificity of action on the proteins of the neuroexocytosis apparatus [1-5]. The 150-kDa proenzymes of bontoxilysin are processed to disulfide-linked subunits of 100 and 50 kDa, the latter being responsible for the endopeptidase activities. Weakly inhibited by captopril, and phosphoramidon. Toxicity is due to action at the neuromuscular junctions that blocks release of acetylcholine, causing flaccid paralysis, in contrast to the spastic paralysis caused by tentoxilysin. In peptidase family M27 (tentoxilysin family)
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 107231-12-9 (not distinguished from EC 3.4.24.68)
References
1. Schiavo, G., Rossetto, O., Catsicas, S., Polverino De Laureto, P., DasGupta, B.R., Benfenati, F. and Montecucco, C. Identification of the nerve-terminal targets of botulinum neurotoxins serotypes A, D and E. J. Biol. Chem. 268 (1993) 23784-23787. [PMID: 8226912]
2. Schiavo, G., Santucci, A., DasGupta, B.R., Mehta, P.P., Jontes, J., Benfenati, F., Wilson, M.C. and Montecucco, C. Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett. 335 (1993) 99-103. [PMID: 8243676]
3. Schiavo, G., Shone, C.C., Rossetto, O., Alexander, F.C.G. and Montecucco, C. Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. J. Biol. Chem. 268 (1993) 11516-11519. [PMID: 8505288]
4. Schiavo, G., Malizio, C., Trimble, W.S., Polverino De Laureto, P., Milan, G., Sugiyama, H., Johnson, E.A. and Montecucco, C. Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond. J. Biol. Chem. 269 (1994) 20213-20216. [PMID: 8051110]
5. Montecucco, C. and Schiavo, G. Mechanism of action of tetanus and botulinum neurotoxins. Mol. Microbiol. 8 (1994) 1-13. [PMID: 7527117]
6. Schiavo, G. and Montecucco, C. Tetanus and botulism neurotoxins. Methods Enzymol. 248 (1995) 643-652. [PMID: 7674951]