1xtg

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[[Image:1xtg.gif|left|200px]]
 
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{{Structure
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==Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25==
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|PDB= 1xtg |SIZE=350|CAPTION= <scene name='initialview01'>1xtg</scene>, resolution 2.10&Aring;
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<StructureSection load='1xtg' size='340' side='right'caption='[[1xtg]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene>
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<table><tr><td colspan='2'>[[1xtg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XTG FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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|GENE= SNAP25, SNAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xtg OCA], [https://pdbe.org/1xtg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xtg RCSB], [https://www.ebi.ac.uk/pdbsum/1xtg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xtg ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xt/1xtg_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xtg ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25'''
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==See Also==
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*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
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*[[Synaptosomal-associated protein|Synaptosomal-associated protein]]
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==Overview==
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__TOC__
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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.
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</StructureSection>
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==About this Structure==
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1XTG is a [[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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XTG OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15592454 15592454]
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[[Category: Clostridium botulinum]]
[[Category: Clostridium botulinum]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Breidenbach, M A.]]
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[[Category: Breidenbach MA]]
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[[Category: Brunger, A T.]]
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[[Category: Brunger AT]]
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[[Category: CL]]
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[[Category: ZN]]
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[[Category: botox]]
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[[Category: botulism]]
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[[Category: exosite]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:14:19 2008''
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Current revision

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

PDB ID 1xtg

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