2qn0: Difference between revisions

Revision as of 15:14, 4 May 2008

Structure of Botulinum neurotoxin serotype C1 light chain protease

OverviewOverview

Clostridial neurotoxins are the causative agents of the neuroparalytic disease botulism and tetanus. They block neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs) SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery. The catalytic component of the clostridial neurotoxins is their light chain (LC), a Zn2+ endopeptidase. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), termed serotype A to G, and tetanus neurotoxin (TeNT). Each of them exhibits unique specificity for their target SNAREs and peptide bond(s) they cleave. The mechanisms of action for substrate recognition and target cleavage are largely unknown. Here, we report structural and biochemical studies of BoNT/C1-LC, which is unique among BoNTs in that it exhibits dual specificity toward both syntaxin and SNAP-25. A distinct pocket (S1') near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin. Mutations of this SNAP-25 residue dramatically reduce enzymatic activity. The remote alpha-exosite that was previously identified in the complex of BoNT/A-LC and SNAP-25 is structurally conserved in BoNT/C1. However, mutagenesis experiments show that the alpha-exosite of BoNT/C1 plays a less stringent role in substrate discrimination in comparison to that of BoNT/A, which could account for its dual substrate specificity.

About this StructureAbout this Structure

2QN0 is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.

ReferenceReference

Structural and biochemical studies of botulinum neurotoxin serotype C1 light chain protease: implications for dual substrate specificity., Jin R, Sikorra S, Stegmann CM, Pich A, Binz T, Brunger AT, Biochemistry. 2007 Sep 18;46(37):10685-93. Epub 2007 Aug 24. PMID:17718519 Page seeded by OCA on Sun May 4 15:14:00 2008

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OCA

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 [[Image:2qn0.jpg|left|200px]]
- {{Structure
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-|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+431'>AC1</scene>
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-|GENE= bont/C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])
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-|DOMAIN=
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-|RELATEDENTRY=[[1xtf|1XTF]], [[2fpq|2FPQ]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qn0 OCA], [http://www.ebi.ac.uk/pdbsum/2qn0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qn0 RCSB]</span>
-}}
 '''Structure of Botulinum neurotoxin serotype C1 light chain protease'''
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 [[Category: Sikorra, S.]]
 [[Category: Stegmann, C M.]]
-[[Category: botulism]]
+[[Category: Botulism]]
-[[Category: neurotoxin]]
+[[Category: Neurotoxin]]
-[[Category: protease]]
+[[Category: Protease]]
-[[Category: snare]]
+[[Category: Snare]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 15:14:00 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:51:10 2008''