View source for 2wy6


==Clostridium perfringens alpha-toxin strain NCTC8237 mutant T74I==
<StructureSection load='2wy6' size='340' side='right'caption='[[2wy6]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wy6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WY6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wy6 OCA], [https://pdbe.org/2wy6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wy6 RCSB], [https://www.ebi.ac.uk/pdbsum/2wy6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wy6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PHLC_CLOP1 PHLC_CLOP1] Bacterial hemolysins are exotoxins that attack blood cell membranes and cause cell rupture. Constitutes an essential virulence factor in gas gangrene. Binds to eukaryotic membranes where it hydrolyzes both phosphatidylcholine and sphingomyelin. The diacylglycerol produced can activate both the arachidonic acid pathway, leading to modulation of the inflammatory response cascade and thrombosis, and protein kinase C, leading to activation of eukaryotic phospholipases and further membrane damage. Acts on human and mouse erythrocytes, but not on rabbit or horse erythrocytes.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wy/2wy6_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2wy6 ConSurf].
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== Publication Abstract from PubMed ==
The alpha-toxin produced by Clostridium perfringens is one of the best-studied examples of a toxic phospholipase C. In this study, a nontoxic mutant protein from C. perfringens strain NCTC8237 in which Thr74 is substituted by isoleucine (T74I) has been characterized and is compared with the toxic wild-type protein. Thr74 is part of an exposed loop at the proposed membrane-interfacing surface of the toxin. The mutant protein had markedly reduced cytotoxic and myotoxic activities. However, this substitution did not significantly affect the catalytic activity towards water-soluble substrate or the overall three-dimensional structure of the protein. The data support the proposed role of the 70-90 loop in the recognition of membrane phospholipids. These findings also provide key evidence in support of the hypothesis that the hydrolysis of both phosphatidylcholine and sphingomyelin are required for the cytolytic and toxic activity of phospholipases.

Comparison of a nontoxic variant of Clostridium perfringens alpha-toxin with the toxic wild-type strain.,Vachieri SG, Clark GC, Alape-Giron A, Flores-Diaz M, Justin N, Naylor CE, Titball RW, Basak AK Acta Crystallogr D Biol Crystallogr. 2010 Oct;66(Pt 10):1067-74. Epub 2010, Sep 18. PMID:20944240<ref>PMID:20944240</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wy6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemolysin 3D structures|Hemolysin 3D structures]]
*[[Phospholipase C|Phospholipase C]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Large Structures]]
[[Category: Basak AK]]
[[Category: Naylor CE]]
[[Category: Vachieri SG]]