Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E.

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.