1xtg

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Revision as of 04:12, 21 November 2007

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spinqualitylabelsall models 1xtg, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25

Overview

Clostridal neurotoxins (CNTs) are the causative agents of the, neuroparalytic diseases botulism and tetanus. CNTs impair neuronal, exocytosis through specific proteolysis of essential proteins called, SNAREs. SNARE assembly into a low-energy ternary complex is believed to, catalyse membrane fusion, precipitating neurotransmitter release; this, process is attenuated in response to SNARE proteolysis. Site-specific, SNARE hydrolysis is catalysed by the CNT light chains, a unique group of, zinc-dependent endopeptidases. The means by which a CNT properly, identifies and cleaves its target SNARE has been a subject of much, speculation; it is thought to use one or more regions of enzyme-substrate, interaction remote from the active site (exosites). Here we report the, first structure of a CNT endopeptidase in complex with its target SNARE at, a resolution of 2.1 A: botulinum neurotoxin serotype A (BoNT/A) protease, bound to human SNAP-25. The structure, together with enzyme kinetic data, reveals an array of exosites that determine substrate specificity., Substrate orientation is similar to that of the general zinc-dependent, metalloprotease thermolysin. We observe significant structural changes, near the toxin's catalytic pocket upon substrate binding, probably serving, to render the protease competent for catalysis. The novel structures of, the substrate-recognition exosites could be used for designing inhibitors, specific to BoNT/A.

About this Structure

1XTG is a Protein complex structure of sequences from Clostridium botulinum and Homo sapiens with ZN and CL as ligands. Full crystallographic information is available from OCA.

Reference

Substrate recognition strategy for botulinum neurotoxin serotype A., Breidenbach MA, Brunger AT, Nature. 2004 Dec 16;432(7019):925-9. Epub 2004 Dec 12. PMID:15592454

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