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3qu8

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Crystal structure of a human cytochrome P450 2B6 (Y226H/K262R) in complex with the inhibitor 4-(4-Nitrobenzyl)pyridine.

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 ==Crystal structure of a human cytochrome P450 2B6 (Y226H/K262R) in complex with the inhibitor 4-(4-Nitrobenzyl)pyridine.==
-<StructureSection load='3qu8' size='340' side='right' caption='[[3qu8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='3qu8' size='340' side='right'caption='[[3qu8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3qu8]] is a 6 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=3QU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QU8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3qu8]] is a 6 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=3QU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QU8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QU:4-(4-NITROBENZYL)PYRIDINE'>3QU</scene>, <scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
+</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>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ibd|3ibd]], [[3qoa|3qoa]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QU:4-(4-NITROBENZYL)PYRIDINE'>3QU</scene>, <scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2B6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3qu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qu8 OCA], [https://pdbe.org/3qu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qu8 RCSB], [https://www.ebi.ac.uk/pdbsum/3qu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qu8 ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>
-<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=3qu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qu8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qu8 RCSB], [http://www.ebi.ac.uk/pdbsum/3qu8 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CP2B6_HUMAN CP2B6_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. Acts as a 1,4-cineole 2-exo-monooxygenase.<ref>PMID:11695850</ref>
+[https://www.uniprot.org/uniprot/CP2B6_HUMAN CP2B6_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. Acts as a 1,4-cineole 2-exo-monooxygenase.<ref>PMID:11695850</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-The biochemical, biophysical, and structural analysis of the cytochrome P450 2B subfamily of enzymes has provided a wealth of information regarding conformational plasticity and substrate recognition. The recent x-ray crystal structure of the drug metabolizing P450 2B6 in complex with 4-(4-chlorophenyl)imidazole (4-CPI) yielded the first atomic view of this human enzyme. However, knowledge of the structural basis of P450 2B6 specificity and inhibition has remained limited. In this study, structures of P450 2B6 were determined in complex with the potent inhibitors 4-benzylpyridine (4-BP) and 4-(4-nitrobenzyl)pyridine (4-NBP). Comparison of the present structures with the previous P450 2B6-4-CPI complex showed that reorientation of side chains of active site residue Phe206 on the F-helix and Phe297 on the I- helix was necessary to accommodate the inhibitors. However, P450 2B6 does not require any major side chain rearrangement to bind 4-NBP compared with 4-BP, nor does the enzyme provide hydrogen-bonding partners for the polar nitro group of 4-NBP within the hydrophobic active site. Additionally, based on these new structures, substitution of residue 172 with histidine as observed in the single nucleotide polymorphism Q172H and in P450 2B4 may contribute to a hydrogen bonding network connecting the E- and I-helices, thereby stabilizing active site residues on the I-helix. These results provide insight into the role of active site side chains upon inhibitor binding and indicate that the recognition of the benzylpyridines in the closed conformation structure of P450 2B6 is based solely on hydrophobicity, size, and shape.
-Structures of Cytochrome P450 2B6 Bound to 4-Benzylpyridine and 4-(4-Nitrobenzyl)pyridine: Insight into Inhibitor Binding and Rearrangement of Active Site Side Chains.,Shah MB, Pascual J, Zhang Q, Stout CD, Halpert JR Mol Pharmacol. 2011 Aug 29. PMID:21875942<ref>PMID:21875942</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
 ==See Also==
-*[[Cytochrome P450|Cytochrome P450]]
+*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
 == References ==
 <references/>
@@ Line 27: / Line 18: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Unspecific monooxygenase]]
+[[Category: Large Structures]]
-[[Category: Halpert, J R]]
+[[Category: Halpert JR]]
-[[Category: Pascual, J]]
+[[Category: Pascual J]]
-[[Category: Shah, M B]]
+[[Category: Shah MB]]
-[[Category: Stout, C D]]
+[[Category: Stout CD]]
-[[Category: Cyp2b6]]
-[[Category: Cytochrome p450 2b6]]
-[[Category: Endoplasmic reticulum]]
-[[Category: Heme]]
-[[Category: Iron]]
-[[Category: Membrane]]
-[[Category: Membrane protein]]
-[[Category: Metal binding]]
-[[Category: Microsome]]
-[[Category: Monooxygenase]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
-[[Category: P450]]
-[[Category: Phosphoprotein]]

3qu8

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Current revision

Crystal structure of a human cytochrome P450 2B6 (Y226H/K262R) in complex with the inhibitor 4-(4-Nitrobenzyl)pyridine.

Structural highlights

Function

See Also

References

Contents

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