2qn0
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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 with as ligand. 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):10685-10693. Epub 2007 Aug 24. PMID:17718519
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