Protease Activity of the Botulinum Neurotoxins

Research output: Chapters, Conference Papers, Creative and Literary Works (RGC: 12, 32, 41, 45)12_Chapter in an edited book (Author)peer-review

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Author(s)

Detail(s)

Original languageEnglish
Title of host publicationMolecular Aspects of Botulinum Neurotoxin
EditorsKeith A. Foster
PublisherSpringer New York
Chapter8
Pages171-189
Volume4
ISBN (Electronic)978-1-4614-9454-6
ISBN (Print)978-1-4614-9453-9
Publication statusPublished - 2014
Externally publishedYes

Publication series

NameCurrent Topics in Neurotoxicity

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.

Research Area(s)

  • "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

Citation Format(s)

Protease Activity of the Botulinum Neurotoxins. / Chen, Sheng; Barbieri, Joseph T.

Molecular Aspects of Botulinum Neurotoxin. ed. / Keith A. Foster. Vol. 4 Springer New York, 2014. p. 171-189 (Current Topics in Neurotoxicity).

Research output: Chapters, Conference Papers, Creative and Literary Works (RGC: 12, 32, 41, 45)12_Chapter in an edited book (Author)peer-review