1w0g: Difference between revisions

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-[[Image:1w0g.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1w0g", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_1w0g|  PDB=1w0g  |  SCENE=  }}
-'''CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4'''
+==Crystal structure of human cytochrome P450 3A4==
+<StructureSection load='1w0g' size='340' side='right'caption='[[1w0g]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1w0g]] 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=1W0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0G 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]] 2.73&#8491;</td></tr>
+<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=MYT:METYRAPONE'>MYT</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=1w0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0g OCA], [https://pdbe.org/1w0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0g RCSB], [https://www.ebi.ac.uk/pdbsum/1w0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0g ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+== 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/w0/1w0g_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=1w0g ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-==Overview==
+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>
-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.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-W0G is a [[Single protein]] structure of 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=1W0G OCA].
+</div>
+<div class="pdbe-citations 1w0g" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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://www.ncbi.nlm.nih.gov/pubmed/15256616 15256616]
+*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Angove, H C.]]
+[[Category: Angove HC]]
-[[Category: Cosme, J.]]
+[[Category: Cosme J]]
-[[Category: Day, P J.]]
+[[Category: Day PJ]]
-[[Category: Jhoti, H.]]
+[[Category: Jhoti H]]
-[[Category: Tickle, I J.]]
+[[Category: Tickle IJ]]
-[[Category: Vinkovic, D M.]]
+[[Category: Vinkovic DM]]
-[[Category: Vonrhein, C.]]
+[[Category: Vonrhein C]]
-[[Category: Ward, A.]]
+[[Category: Ward A]]
-[[Category: Williams, P A.]]
+[[Category: Williams PA]]
-[[Category: Cytochrome p450]]
-[[Category: Electron transport]]
-[[Category: Monooxygenase]]
-[[Category: Nifedipine oxidase]]
-[[Category: Oxidoreductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 12:59:21 2008''