Protease activity of the botulinum neurotoxins

Sheng Chen, Joseph T. Barbieri

Research output: Chapter in book / Conference proceedingChapter in an edited book (as author)Academic researchpeer-review

1 Citation (Scopus)

Abstract

The flaccid pathology associated with intoxication by the botulinum neurotoxins (BoNTs) is the result of the association of the toxin to neuronal-specific host receptors and the cleavage of neuronal substrates, soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) proteins. Each of the seven serotypes of BoNTs (A-G) targets a specific neuronal SNARE protein(s) for cleavage. Neuronal SNARE proteins function in the binding and fusion of neurotransmitter vesicles with a host membrane, and SNARE protein cleavage by the BoNTs disrupts the fusion process leading to host paralysis. The mechanism that BoNTs utilize to bind and cleave the SNARE proteins involves recognizing an extended substrate surface to allow the BoNTs to efficiently cleave the coiled SNARE protein substrate. BoNT serotypes comprise natural variants termed subtypes, which extends the complexity and potential pathology of the BoNTs. Understanding the mechanisms of BoNT action provides tools towards the development of strategies to identify novel small-molecule inhibitors of BoNT catalysis and to extend the use of BoNTs as therapeutic agents.
Original languageEnglish
Title of host publicationMolecular Aspects of Botulinum Neurotoxin
PublisherSpringer New York
Pages171-189
Number of pages19
ISBN (Electronic)9781461494546
ISBN (Print)9781461494539
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • "Pocket" model
  • Belt region
  • Botulinum neurotoxin
  • Exosites
  • Scissile bond
  • SNARE proteins
  • Synaptobrevin
  • Synaptosomal-associated protein of 25 kDa (SNAP- 25)
  • Syntaxin
  • t-SNARE
  • v-SNARE
  • Vesicle associated membrane protein (VAMP)
  • Zincmetalloprotease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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