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FUNCTION Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.CATALYTIC ACTIVITY Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.COFACTOR Binds 1 zinc ion per subunit.SUBUNIT Disulfide-linked heterodimer of a light chain (L) and a heavy chain (H).PHARMACEUTICAL Available under the name BOTOX (Allergan) for the treatment of strabismus and blepharospasm associated with dystonia and cervical dystonia. Also used for the treatment of hemifacial spasm and a number of other neurological disorders characterized by abnormal muscle contraction.MISCELLANEOUS There are seven antigenically distinct forms of botulinum neurotoxin: Types A, B, C1, D, E, F, and G.SIMILARITY Belongs to the peptidase M27 family.
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bna
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UniProt:P10845 botA,
atx,
botA
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