1xtf

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[[Image:1xtf.gif|left|200px]]
 
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{{Structure
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==neurotoxin BoNT/A E224Q Y366F mutant==
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|PDB= 1xtf |SIZE=350|CAPTION= <scene name='initialview01'>1xtf</scene>, resolution 2.2&Aring;
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<StructureSection load='1xtf' size='340' side='right'caption='[[1xtf]], [[Resolution|resolution]] 2.20&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>
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<table><tr><td colspan='2'>[[1xtf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XTF 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]] 2.2&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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|DOMAIN=
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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=1xtf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xtf OCA], [https://pdbe.org/1xtf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xtf RCSB], [https://www.ebi.ac.uk/pdbsum/1xtf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xtf ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1xtg|1XTG]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xtf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xtf OCA], [http://www.ebi.ac.uk/pdbsum/1xtf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xtf RCSB]</span>
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== Function ==
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}}
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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/1xtf_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=1xtf ConSurf].
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<div style="clear:both"></div>
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'''neurotoxin BoNT/A E224Q Y366F mutant'''
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==See Also==
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*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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==About this Structure==
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1XTF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XTF 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]]
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[[Category: Single protein]]
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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: botulism]]
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[[Category: neurotoxin]]
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[[Category: zinc endopeptidase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:54:25 2008''
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Current revision

neurotoxin BoNT/A E224Q Y366F mutant

PDB ID 1xtf

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