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4nz2

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==Crystal structure of CYP2C9 in complex with an inhibitor==
==Crystal structure of CYP2C9 in complex with an inhibitor==
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<StructureSection load='4nz2' size='340' side='right' caption='[[4nz2]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
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<StructureSection load='4nz2' size='340' side='right'caption='[[4nz2]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4nz2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NZ2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4nz2]] 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=4NZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NZ2 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QJ:(2R)-N-{4-[(3-BROMOPHENYL)SULFONYL]-2-CHLOROPHENYL}-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANAMIDE'>2QJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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]] 2.45&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ny4|4ny4]]</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=2QJ:(2R)-N-{4-[(3-BROMOPHENYL)SULFONYL]-2-CHLOROPHENYL}-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANAMIDE'>2QJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nz2 OCA], [http://pdbe.org/4nz2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nz2 RCSB], [http://www.ebi.ac.uk/pdbsum/4nz2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nz2 ProSAT]</span></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=4nz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nz2 OCA], [https://pdbe.org/4nz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nz2 RCSB], [https://www.ebi.ac.uk/pdbsum/4nz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nz2 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/CP2C9_HUMAN CP2C9_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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
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[https://www.uniprot.org/uniprot/CP2C9_HUMAN CP2C9_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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Cytochrome P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects.
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Structure-based ligand design to overcome CYP inhibition in drug discovery projects.,Branden G, Sjogren T, Schnecke V, Xue Y Drug Discov Today. 2014 Jul;19(7):905-911. doi: 10.1016/j.drudis.2014.03.012., Epub 2014 Mar 16. PMID:24642031<ref>PMID:24642031</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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<div class="pdbe-citations 4nz2" style="background-color:#fffaf0;"></div>
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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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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Branden, G]]
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[[Category: Homo sapiens]]
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[[Category: Sjogren, T]]
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[[Category: Large Structures]]
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[[Category: Xue, Y]]
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[[Category: Branden G]]
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[[Category: Cyp2c9]]
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[[Category: Sjogren T]]
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[[Category: Cytochrome p-450]]
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[[Category: Xue Y]]
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[[Category: Drug metabolism]]
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[[Category: Inhibitor]]
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[[Category: Monooxygenase]]
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[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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[[Category: Structure-based drug design]]
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Current revision

Crystal structure of CYP2C9 in complex with an inhibitor

PDB ID 4nz2

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