Substrate residues N-terminal to the cleavage site of botulinum type B neurotoxin play a role in determining the specificity of its endopeptidase activity.
Clostridium botulinum type B neurotoxin is a highly specific zinc-endopeptidase which cleaves vesicle-associated membrane protein (VAMP/synaptobrevin), a critical component of the vesicle docking/fusion mechanism. In this study, substrate residues flanking the N-terminal side of the cleavage site are shown to play a key role in enzyme substrate recognition. Two aspartate residues in this region are identified as critical determinants of the neurotoxin's specificity. These findings are discussed in relation to the mechanism by which botulinum type B neurotoxin cleaves its substrate.
Wictome
M
M
Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire, UK.
Rossetto
O
O
Montecucco
C
C
Shone
C C
CC
D000595:Amino Acid Sequence; D001665:Binding Sites; D001905:Botulinum Toxins / Q000378:metabolism*; D004220:Disulfides; D010450:Endopeptidases / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D050683:R-SNARE Proteins; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004220:Disulfides; D008565:Membrane Proteins; D050683:R-SNARE Proteins; D010450:Endopeptidases; D001905:Botulinum Toxins