1w0f

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[[Image:1w0f.png|left|200px]]
 
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{{STRUCTURE_1w0f| PDB=1w0f | SCENE= }}
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==Crystal structure of human cytochrome P450 3A4==
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<StructureSection load='1w0f' size='340' side='right'caption='[[1w0f]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1w0f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0F FirstGlance]. <br>
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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]] 2.65&#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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</scene></td></tr>
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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=1w0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0f OCA], [https://pdbe.org/1w0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0f RCSB], [https://www.ebi.ac.uk/pdbsum/1w0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0f ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CP3A4_HUMAN CP3A4_HUMAN] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.<ref>PMID:11159812</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/w0/1w0f_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=1w0f 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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Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.
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===CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4===
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Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone.,Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti H Science. 2004 Jul 30;305(5684):683-6. Epub 2004 Jul 15. PMID:15256616<ref>PMID:15256616</ref>
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{{ABSTRACT_PUBMED_15256616}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1w0f" style="background-color:#fffaf0;"></div>
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[[1w0f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0F OCA].
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==See Also==
==See Also==
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*[[Cytochrome P450|Cytochrome P450]]
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*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015256616</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Angove, H C.]]
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[[Category: Large Structures]]
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[[Category: Cosme, J.]]
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[[Category: Angove HC]]
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[[Category: Day, P J.]]
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[[Category: Cosme J]]
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[[Category: Jhoti, H.]]
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[[Category: Day PJ]]
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[[Category: Tickle, I J.]]
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[[Category: Jhoti H]]
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[[Category: Vinkovic, D M.]]
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[[Category: Tickle IJ]]
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[[Category: Vonrhein, C.]]
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[[Category: Vinkovic DM]]
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[[Category: Ward, A.]]
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[[Category: Vonrhein C]]
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[[Category: Williams, P A.]]
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[[Category: Ward A]]
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[[Category: Cytochrome p450]]
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[[Category: Williams PA]]
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[[Category: Electron transport]]
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[[Category: Monooxygenase]]
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[[Category: Nifedipine oxidase]]
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[[Category: Oxidoreductase]]
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Current revision

Crystal structure of human cytochrome P450 3A4

PDB ID 1w0f

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