title: Tetanus and botulism neurotoxins: a novel group of zinc-endopeptidases.
abstract: Tetanus and botulinum neurotoxins are produced by bacteria of the genus Clostridium and cause the paralytic syndromes of tetanus and botulism with a persistent inhibition of neurotransmitter release at central and peripheral synapses, respectively. These neurotoxins consist of two disulfide-linked polypeptides: H (100 kDa) is responsible for neurospecific binding and cell penetration of L(50 kDa), a zinc-endopeptidase specific for three protein subunits of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxins serotypes B, D, F, and G cleave at single sites, which differ for each neurotoxin. VAMP/synaptobrevin, a membrane protein of the synaptic vesicles. Botulinum A and E neurotoxins cleave SNAP-25, a protein of the presynaptic membrane, at two different carboxyl-terminal peptide bonds. Serotype C cleaves specifically syntaxin, another protein of the nerve plasmalemma. The target specificity of these metallo-proteinases relies on a double recognition of their substrates based on interactions with the cleavage site and with a non contiguous segment that contains a structural motif common to VAMP, SNAP-25 and syntaxin.
authors.affiliation: Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Universita di Padovà, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tonello
authors.forename: S
authors.initials: S
authors.lastname: Morante
authors.forename: O
authors.initials: O
authors.lastname: Rossetto
authors.forename: G
authors.initials: G
authors.lastname: Schiavo
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000737:chemistry*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013744:Tetanus Toxin / Q000737:chemistry*
chemical_list: D009419:Nerve Tissue Proteins; D013744:Tetanus Toxin; D008666:Metalloendopeptidases; D001905:Botulinum Toxins