title: The role of exoproteases in governing intraneuronal metabolism of botulinum toxin.
abstract: Botulinum toxin type A has a long duration of action, and thus it can block transmitter release for several weeks to several months. However, little is known about the precise mechanism that accounts for termination of toxin action. Therefore, experiments were done to gauge the effects of aminopeptidases and carboxypeptidases on the structure and function of the toxin. Exoproteases were added to the holotoxin, the native light chain, and a recombinant light chain. Treated toxin and light chain were examined for their effects on neuromuscular transmission and on isolated substrate. The data showed that aminopeptidase attack did not alter the N-terminus of the toxin/light chain, nor did it produce losses in biological activity. Carboxypeptidase attack did alter the C-terminus of the light chain, but not sufficiently to alter biological activity. The data suggest that the tertiary structure of the light chain confers upon the molecule substantial resistance to exoproteases.
authors.affiliation: Department of Medicine, Jefferson Medical College, Philadelphia, PA, USA. Lance.Simpson@jefferson.edu
authors.forename: Lance L
authors.initials: LL
authors.lastname: Simpson
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Maksymowych
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kouguchi
authors.forename: Garrett
authors.initials: G
authors.lastname: Dubois
authors.forename: Roop S
authors.initials: RS
authors.lastname: Bora
authors.forename: Suresh
authors.initials: S
authors.lastname: Joshi
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism*; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002268:Carboxypeptidases / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002268:Carboxypeptidases; D000626:Aminopeptidases; D019274:Botulinum Toxins, Type A