2x5w

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{{Seed}}
 
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[[Image:2x5w.jpg|left|200px]]
 
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==X-ray structure of Mycobacterium tuberculosis cytochrome P450 CYP125 in complex with substrate cholest-4-en-3-one==
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The line below this paragraph, containing "STRUCTURE_2x5w", creates the "Structure Box" on the page.
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<StructureSection load='2x5w' size='340' side='right'caption='[[2x5w]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2x5w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X5W FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.58&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=K2B:(8ALPHA,9BETA)-CHOLEST-4-EN-3-ONE'>K2B</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2x5w| PDB=2x5w | SCENE= }}
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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=2x5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x5w OCA], [https://pdbe.org/2x5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x5w RCSB], [https://www.ebi.ac.uk/pdbsum/2x5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x5w ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CP125_MYCTU CP125_MYCTU] Catalyzes the C-27 hydroxylation of cholest-4-en-3-one and cholesterol and subsequently oxidizes the alcohol of the former to the cholest-4-en-3-one-27-oic acid via the aldehyde intermediate. Not required to incorporate the cholesterol side-chain carbon atoms into cellular lipids.<ref>PMID:19846551</ref> <ref>PMID:20545858</ref>
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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/x5/2x5w_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=2x5w ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The infectivity and persistence of Mycobacterium tuberculosis requires the utilization of host cell cholesterol. We have examined the specific role of cytochrome P450 CYP125A1 in the cholesterol degradation pathway using genetic, biochemical and high-resolution mass spectrometric approaches. The analysis of lipid profiles from cells grown on cholesterol revealed that CYP125A1 is required to incorporate the cholesterol side-chain carbon atoms into cellular lipids, as evidenced by an increase in the mass of the methyl-branched phthiocerol dimycocerosates. We observed that cholesterol-exposed cells lacking CYP125A1 accumulate cholest-4-en-3-one, suggesting that this is a physiological substrate for this enzyme. Reconstitution of enzymatic activity with spinach ferredoxin and ferredoxin reductase revealed that recombinant CYP125A1 indeed binds both cholest-4-en-3-one and cholesterol, efficiently hydroxylates both of them at C-27, and then further oxidizes 27-hydroxycholest-4-en-3-one to cholest-4-en-3-one-27-oic acid. We determined the X-ray structure of cholest-4-en-3-one-bound CYP125A1 at a resolution of 1.58 A. CYP125A1 is essential for growth of CDC1551 in media containing cholesterol or cholest-4-en-3-one. In its absence, the latter compound is toxic for both CDC1551 and H37Rv when added with glycerol as a second carbon source. CYP125A1 is a key enzyme in cholesterol metabolism and plays a crucial role in circumventing the deleterious effect of cholest-4-en-3-one.
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===X-RAY STRUCTURE OF CYP125A1 FROM M. TUBERCULOSIS BOUND TO THE SUBSTRATE CHOLEST-4-EN-3-ONE===
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Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one.,Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR Mol Microbiol. 2010 Aug;77(3):730-42. Epub 2010 Jun 10. PMID:20545858<ref>PMID:20545858</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==About this Structure==
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</div>
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2X5W is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X5W OCA].
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<div class="pdbe-citations 2x5w" style="background-color:#fffaf0;"></div>
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[[Category: Mycobacterium tuberculosis]]
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== References ==
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[[Category: Burlingame, A L.]]
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<references/>
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[[Category: Chow, E D.]]
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__TOC__
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[[Category: Cox, J S.]]
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</StructureSection>
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[[Category: Guan, S.]]
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[[Category: Large Structures]]
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[[Category: Johnston, J B.]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Kells, P M.]]
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[[Category: Burlingame AL]]
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[[Category: Montellano, P R.Ortiz De.]]
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[[Category: Chow ED]]
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[[Category: Ouellet, H.]]
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[[Category: Cox JS]]
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[[Category: Podust, L M.]]
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[[Category: Guan S]]
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[[Category: Cholesterol degradation]]
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[[Category: Johnston JB]]
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[[Category: Metal-binding]]
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[[Category: Kells PM]]
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[[Category: Oxidoreductase]]
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[[Category: Ortiz de Montellano PR]]
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[[Category: Ouellet H]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 16 08:35:51 2010''
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[[Category: Podust LM]]

Current revision

X-ray structure of Mycobacterium tuberculosis cytochrome P450 CYP125 in complex with substrate cholest-4-en-3-one

PDB ID 2x5w

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