Proteolysis of synthetic peptides by type A botulinum neurotoxin.
Type A botulinum neurotoxin catalyzed the hydrolysis of synthetic peptides based on the sequence of the 25-kD synaptosomal protein SNAP-25. In each peptide, the toxin cleaved at a single glutaminyl-arginine bond corresponding to residues 197 and 198 of SNAP-25, confirming earlier reports on the enzymatic specificity of the toxin in synaptosomal preparations. Metal chelators inhibited catalysis, consistent with a metalloprotease activity. In contrast to tetanus toxin and other botulinum toxin serotypes, type A toxin hydrolyzed relatively short, 17- to 20-residue peptides. In the substrates, SNAP-25 residue 202 and one or more of residues 187-191 were required for efficient hydrolysis, but residues 167-186 and 203-206 were not. The highest rates of hydrolysis were found when the C-terminal residues of the peptides were amidated.
Schmidt
J J
JJ
Toxinology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA.
Bostian
K A
KA
D000577:Amides / Q000378:metabolism; D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004229:Dithiothreitol / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D013379:Substrate Specificity; D050825:Synaptosomal-Associated Protein 25; D013744:Tetanus Toxin / Q000378:metabolism
D000577:Amides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D050825:Synaptosomal-Associated Protein 25; D013744:Tetanus Toxin; D001905:Botulinum Toxins; D004229:Dithiothreitol