title: Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E.
abstract: Botulinum neurotoxins are metalloproteins with one zinc atom bound to the zinc binding motif of zinc endopeptidases. Here we show that botulinum neurotoxin serotypes A, D, and E are zinc endoproteases specific for components of the synaptic vesicle docking and fusion complex. Serotypes A and E cleave SNAP-25, a 25-kDa protein of the synaptic terminal, while serotype D is specific for VAMP/synaptobrevin, a membrane protein of synaptic vesicles. Both rat brain VAMP isoforms are cleaved at a single Lys-Leu peptide bond. The proteolytic activity of these neurotoxins is inhibited by EDTA and captopril.
authors.affiliation: Centro Consiglio Nazionale delle Ricerche Biomembrane, Università di Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Schiavo
authors.forename: O
authors.initials: O
authors.lastname: Rossetto
authors.forename: S
authors.initials: S
authors.lastname: Catsicas
authors.forename: P
authors.initials: P
authors.lastname: Polverino de Laureto
authors.forename: B R
authors.initials: BR
authors.lastname: DasGupta
authors.forename: F
authors.initials: F
authors.lastname: Benfenati
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism*; D006868:Hydrolysis; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D050683:R-SNARE Proteins; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D001905:Botulinum Toxins