1xtg
From Proteopedia
(New page: 200px<br /><applet load="1xtg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xtg, resolution 2.10Å" /> '''Crystal structure of...) |
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| - | [[Image:1xtg.gif|left|200px]]<br /><applet load="1xtg" size=" | + | [[Image:1xtg.gif|left|200px]]<br /><applet load="1xtg" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xtg, resolution 2.10Å" /> | caption="1xtg, resolution 2.10Å" /> | ||
'''Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25'''<br /> | '''Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Clostridal neurotoxins (CNTs) are the causative agents of the | + | 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== | ==About this Structure== | ||
| - | 1XTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1XTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XTG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Breidenbach, M | + | [[Category: Breidenbach, M A.]] |
| - | [[Category: Brunger, A | + | [[Category: Brunger, A T.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: exosites]] | [[Category: exosites]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:58:29 2008'' |
Revision as of 13:58, 21 February 2008
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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 and 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
Page seeded by OCA on Thu Feb 21 15:58:29 2008
Categories: Clostridium botulinum | Homo sapiens | Protein complex | Breidenbach, M A. | Brunger, A T. | CL | ZN | Botox | Botulism | Exosites
