1w0e

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(New page: 200px<br /> <applet load="1w0e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1w0e, resolution 2.8&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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[[Image:1w0e.gif|left|200px]]<br />
 
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<applet load="1w0e" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1w0e, resolution 2.8&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4'''<br />
 
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==Overview==
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==Crystal structure of human cytochrome P450 3A4==
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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 ... [[http://ispc.weizmann.ac.il/pmbin/getpm?15256616 (full description)]]
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<StructureSection load='1w0e' size='340' side='right'caption='[[1w0e]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1w0e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The October 2006 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Cytochrome p450'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2006_10 10.2210/rcsb_pdb/mom_2006_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0E 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]] 2.8&#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></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=1w0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0e OCA], [https://pdbe.org/1w0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0e RCSB], [https://www.ebi.ac.uk/pdbsum/1w0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0e 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/w0/1w0e_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=1w0e 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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==About this Structure==
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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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1W0E is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with HEM as [[http://en.wikipedia.org/wiki/ligand ligand]]. The following page contains interesting information on the relation of 1W0E with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb82_1.html Cytochrome p450]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W0E OCA]].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15256616 15256616]
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</div>
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<div class="pdbe-citations 1w0e" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Cytochrome p450]]
[[Category: Cytochrome p450]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Angove, H.C.]]
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[[Category: RCSB PDB Molecule of the Month]]
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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: HEM]]
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[[Category: Williams PA]]
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[[Category: cytochrome p450]]
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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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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Oct 29 20:43:40 2007''
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Current revision

Crystal structure of human cytochrome P450 3A4

PDB ID 1w0e

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