1kho

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[[Image:1kho.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure Analysis of Clostridium perfringens alpha-Toxin Isolated from Avian Strain SWCP==
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|PDB= 1kho |SIZE=350|CAPTION= <scene name='initialview01'>1kho</scene>, resolution 2.4&Aring;
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<StructureSection load='1kho' size='340' side='right'caption='[[1kho]], [[Resolution|resolution]] 2.40&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'>[[1kho]] is a 2 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=1KHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KHO 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]] 2.4&#8491;</td></tr>
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|GENE= CPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1502 Clostridium perfringens])
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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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}}
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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=1kho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kho OCA], [https://pdbe.org/1kho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kho RCSB], [https://www.ebi.ac.uk/pdbsum/1kho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kho ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PHLC_CLOPF PHLC_CLOPF] 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, causing cell rupture. 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.
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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/kh/1kho_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=1kho ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure Analysis of Clostridium perfringens alpha-Toxin Isolated from Avian Strain SWCP'''
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==See Also==
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*[[Hemolysin 3D structures|Hemolysin 3D structures]]
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*[[Phospholipase C|Phospholipase C]]
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==Overview==
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__TOC__
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Clostridium perfringens alpha-toxin is a 370-residue, zinc-dependent, phospholipase C that is the key virulence determinant in gas gangrene. It is also implicated in the pathogenesis of sudden death syndrome in young animals and necrotic enteritis in chickens. Previously characterized alpha-toxins from different strains of C. perfringens are almost identical in sequence and biochemical properties. We describe the cloning, nucleotide sequencing, expression, characterization, and crystal structure of alpha-toxin from an avian strain, SWan C. perfringens (SWCP), which has a large degree of sequence variation and altered substrate specificity compared to these strains. The structure of alpha-toxin from strain CER89L43 has been previously reported in open (active site accessible to substrate) and closed (active site obscured by loop movements) conformations. The SWCP structure is in an open-form conformation, with three zinc ions in the active site. This is the first example of an open form of alpha-toxin crystallizing without the addition of divalent cations to the crystallization buffer, indicating that the protein can retain three zinc ions bound in the active site. The topology of the calcium binding site formed by residues 269, 271, 336, and 337, which is essential for membrane binding, is significantly altered in comparison with both the open and closed alpha-toxin structures. We are able to relate these structural changes to the different substrate specificity and membrane binding properties of this divergent alpha-toxin. This will provide essential information when developing an effective vaccine that will protect against C. perfringens infection in a wide range of domestic livestock.
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</StructureSection>
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==About this Structure==
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1KHO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KHO OCA].
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==Reference==
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The first strain of Clostridium perfringens isolated from an avian source has an alpha-toxin with divergent structural and kinetic properties., Justin N, Walker N, Bullifent HL, Songer G, Bueschel DM, Jost H, Naylor C, Miller J, Moss DS, Titball RW, Basak AK, Biochemistry. 2002 May 21;41(20):6253-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12009886 12009886]
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[[Category: Clostridium perfringens]]
[[Category: Clostridium perfringens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Basak, A K.]]
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[[Category: Basak AK]]
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[[Category: Justin, N.]]
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[[Category: Justin N]]
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[[Category: Moss, D S.]]
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[[Category: Moss DS]]
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[[Category: Titball, R W.]]
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[[Category: Titball RW]]
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[[Category: ZN]]
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[[Category: c-terminal beta-sheet]]
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[[Category: n-terminal alpha-helix]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:17:37 2008''
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Current revision

Crystal Structure Analysis of Clostridium perfringens alpha-Toxin Isolated from Avian Strain SWCP

PDB ID 1kho

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