1XTG
Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25
Summary for 1XTG
| Entry DOI | 10.2210/pdb1xtg/pdb |
| Related | 1XTF |
| Descriptor | NEUROTOXIN BONT/A, Synaptosomal-associated protein 25, ZINC ION, ... (5 entities in total) |
| Functional Keywords | botox, botulism, exosites, toxin |
| Biological source | Clostridium botulinum More |
| Cellular location | Cytoplasm, perinuclear region : P60880 |
| Total number of polymer chains | 2 |
| Total formula weight | 55396.33 |
| Authors | Breidenbach, M.A.,Brunger, A.T. (deposition date: 2004-10-21, release date: 2004-12-21, Last modification date: 2024-02-14) |
| Primary citation | Breidenbach, M.A.,Brunger, A.T. Substrate recognition strategy for botulinum neurotoxin serotype A Nature, 432:925-929, 2004 Cited by PubMed Abstract: 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. PubMed: 15592454DOI: 10.1038/nature03123 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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