Mechanism of substrate recognition by botulinum neurotoxin serotype A.

Mechanism of substrate recognition by botulinum neurotoxin serotype A. Research Abstract Details 

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Mechanism of substrate recognition by botulinum neurotoxin serotype A. Abstract Text:

Sheng Chen,Jung-Ja P Kim,Joseph T Barbieri,

Botulinum neurotoxins (BoNTs) are zinc proteases that cleave SNARE proteins to elicit flaccid paralysis by inhibiting neurotransmitter-carrying vesicle fusion to the plasma membrane of peripheral neurons. Unlike other zinc proteases, BoNTs recognize extended regions of SNAP25 for cleavage; however, the molecular basis for this extended substrate recognition is unclear. Here, we define a multistep mechanism for recognition and cleavage of SNAP25 by BoNT/A. SNAP25 initially binds along the belt region of BoNT/A, which aligns the P5 residue to the S5 pocket at the periphery of the active site. Although the exact order of each step of recognition of SNAP25 by BoNT/A at the active site is not clear, the initial binding could subsequently orient the P4'-residue of SNAP25 to form a salt bridge with the S4'-residue, which opens the active site allowing the P1'-residue access to the S1'-pocket. Subsequent hydrophobic interactions between the P3 residue of SNAP25 and the S3 pocket optimize alignment of the scissile bond for cleavage. This explains how the BoNTs recognize and cleave specific coiled SNARE substrates and provides insight into the development of inhibitors to prevent botulism.

Mechanism of substrate recognition by botulinum neurotoxin serotype A. Publishing Authors By Initials

S Chen,JJ Kim,JT Barbieri,

For similar proteins: membrane proteins: membrane fusion proteins: snare proteins: q-snare proteins: qb-snare proteins: synaptosomal-associated protein 25 research abstracts see: proteins: membrane proteins: membrane fusion proteins: snare proteins: q-snare proteins: qb-snare proteins: synaptosomal-associated protein 25 research

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Mechanism of substrate recognition by botulinum neurotoxin serotype A. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 9621-7

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 23

MONTH: 01

YEAR: 2007

Mechanism of substrate recognition by botulinum neurotoxin serotype A. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Mechanism of substrate recognition by botulinum neurotoxin serotype A. Keywords Mesh Terms:

KEYWORDS: Synaptosomal-Associated Protein 25

MESH TERMS: metabolism

Chemical & Substance for Abstract: Mechanism of substrate recognition by botulinum neurotoxin serotype A. Information

Substance Name: Synaptosomal-Associated Protein 25

Registry Number: 0

Grant and Affiliation Information for Mechanism of substrate recognition by botulinum neurotoxin serotype A.

AFFILIATION: Department of Microbiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Country: United States

AGENCY: United States NIAID

GRANT: U54 AI057153

ACRONYM: AI

MEDLINETA: J Biol Chem

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