2nnh

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[[Image:2nnh.png|left|200px]]
 
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==CYP2C8dH complexed with 2 molecules of 9-cis retinoic acid==
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The line below this paragraph, containing "STRUCTURE_2nnh", creates the "Structure Box" on the page.
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<StructureSection load='2nnh' size='340' side='right'caption='[[2nnh]], [[Resolution|resolution]] 2.60&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'>[[2nnh]] is a 2 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=2NNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NNH 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]] 2.6&#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=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2nnh| PDB=2nnh | 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=2nnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nnh OCA], [https://pdbe.org/2nnh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nnh RCSB], [https://www.ebi.ac.uk/pdbsum/2nnh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nnh ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CP2C8_HUMAN CP2C8_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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).<ref>PMID:7574697</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/nn/2nnh_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=2nnh 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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Although a crystal structure and a pharmacophore model are available for cytochrome P450 2C8, the role of protein flexibility and specific ligand-protein interactions that govern substrate binding are poorly understood. X-ray crystal structures of P450 2C8 complexed with montelukast (2.8 A), troglitazone (2.7 A), felodipine (2.3 A), and 9-cis-retinoic acid (2.6 A) were determined to examine ligand-protein interactions for these chemically diverse compounds. Montelukast is a relatively large anionic inhibitor that exhibits a tripartite structure and complements the size and shape of the active-site cavity. The inhibitor troglitazone occupies the upper portion of the active-site cavity, leaving a substantial part of the cavity unoccupied. The smaller neutral felodipine molecule is sequestered with its dichlorophenyl group positioned close to the heme iron, and water molecules fill the distal portion of the cavity. The structure of the 9-cis-retinoic acid complex reveals that two substrate molecules bind simultaneously in the active site of P450 2C8. A second molecule of 9-cis-retinoic acid is located above the proximal molecule and can restrain the position of the latter for more efficient oxygenation. Solution binding studies do not discriminate between cooperative and noncooperative models for multiple substrate binding. The complexes with structurally distinct ligands further demonstrate the conformational adaptability of active site-constituting residues, especially Arg-241, that can reorient in the active-site cavity to stabilize a negatively charged functional group and define two spatially distinct binding sites for anionic moieties of substrates.
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===CYP2C8dH complexed with 2 molecules of 9-cis retinoic acid===
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Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid.,Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF J Biol Chem. 2008 Jun 20;283(25):17227-37. Epub 2008 Apr 15. PMID:18413310<ref>PMID:18413310</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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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_18413310}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2nnh" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 18413310 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18413310}}
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==About this Structure==
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[[2nnh]] is a 2 chain structure of [[Cytochrome P450]] 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=2NNH OCA].
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==See Also==
==See Also==
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*[[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:18413310</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: Unspecific monooxygenase]]
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[[Category: Large Structures]]
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[[Category: Johnson, E F.]]
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[[Category: Johnson EF]]
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[[Category: Schoch, G A.]]
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[[Category: Schoch GA]]
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[[Category: Stout, C D.]]
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[[Category: Stout CD]]
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[[Category: Yano, J K.]]
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[[Category: Yano JK]]
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[[Category: 9-cis retinoic acid]]
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[[Category: Cyp2c8]]
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[[Category: Electron transport]]
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[[Category: Human p450 2c8]]
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[[Category: Monooxygenase]]
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[[Category: Oxidoreductase]]
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[[Category: Palmitic acid]]
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[[Category: Panretin]]
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[[Category: Substrate complex]]
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Current revision

CYP2C8dH complexed with 2 molecules of 9-cis retinoic acid

PDB ID 2nnh

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