Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E.

Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Research Abstract Details 

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Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Abstract Text:

Sheng Chen,Joseph T Barbieri,

Botulinum neurotoxins (BoNTs) are zinc proteases that cleave SNARE proteins to elicit flaccid paralysis by inhibiting the fusion of neurotransmitter-carrying vesicles to the plasma membrane of peripheral neurons. There are seven serotypes of BoNT, termed A-G. The molecular basis for SNAP25 recognition and cleavage by BoNT serotype E is currently unclear. Here we define the multiple pocket recognition of SNAP25 by LC/E. The initial recognition of SNAP25 is mediated by the binding of the B region of SNAP25 to the substrate-binding (B) region of LC/E comprising Leu166, Arg167, Asp127, Ala128, Ser129, and Ala130. The mutations at these residues affected substrate binding and catalysis. Three additional residues participate in scissile bond cleavage of SNAP25 by LC/E. The P3 site residues, Ile178, of SNAP25 interacted with the S3 pocket in LC/E through hydrophobic interactions. The S3 pocket included Ile47, Ile164, and Ile182 and appeared to align the P1' and P2 residues of SNAP25 with the S1' and S2 pockets of LC/E. The S1' pocket of LC/E included three residues, Phe191, Thr159, and Thr208, which contribute hydrophobic and steric interactions with the SNAP25 P1' residue Ile181. The S2 pocket residue of LC/E, Lys224, binds the P2 residue of SNAP25, Asp179, through ionic interactions. Deletion mapping indicates that main chain interaction(s) of residues 182-186 of SNAP25 contribute to substrate recognition by LC/E. Understanding the mechanism for substrate specificity provides insight for the development of inhibitors against the botulinum neurotoxins.

Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Publishing Authors By Initials

S Chen,JT Barbieri,

For similar inorganic chemicals: elements: metals, heavy: zinc research abstracts see: inorganic chemicals: elements: metals, heavy: zinc research

PUBMED ID PMID:

MEDLINE DATE:

Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Journal Published:

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

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 25540-7

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 3

MONTH: 07

YEAR: 2007

Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Keywords Mesh Terms:

KEYWORDS: Zinc

MESH TERMS: metabolism

Chemical & Substance for Abstract: Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. Information

Substance Name: Metalloproteases

Registry Number: EC 3.4.-

Grant and Affiliation Information for Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E.

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

Country: United States

AGENCY: United States NIAID

GRANT: 1-U54-AI-057153

ACRONYM: AI

MEDLINETA: J Biol Chem

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