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3ibd

From Proteopedia

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Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole

Structural highlights

3ibd is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The structure of the K262R genetic variant of human cytochrome P450 2B6 in complex with the inhibitor 4-(4-chlorophenyl)imidazole (4-CPI) has been determined using X-ray crystallography to 2.0-A resolution. Production of diffraction quality crystals was enabled through a combination of protein engineering, chaperone coexpression, modifications to the purification protocol, and the use of unique facial amphiphiles during crystallization. The 2B6-4-CPI complex is virtually identical to the rabbit 2B4 structure bound to the same inhibitor with respect to the arrangement of secondary structural elements and the placement of active site residues. The structure supports prior P450 2B6 homology models based on other mammalian cytochromes P450 and is consistent with the limited site-directed mutagenesis studies on 2B6 and extensive studies on P450 2B4 and 2B1. Although the K262R genetic variant shows unaltered binding of 4-CPI, altered binding affinity, kinetics, and/or product profiles have been previously shown with several other ligands. On the basis of new P450 2B6 crystal structure and previous 2B4 structures, substitutions at residue 262 affect a hydrogen-bonding network connecting the G and H helices, where subtle differences could be transduced to the active site. Docking experiments indicate that the closed protein conformation allows smaller ligands such as ticlopidine to bind to the 2B6 active site in the expected orientation. However, it is unknown whether 2B6 undergoes structural reorganization to accommodate bulkier molecules, as previously inferred from multiple P450 2B4 crystal structures.

Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution.,Gay SC, Shah MB, Talakad JC, Maekawa K, Roberts AG, Wilderman PR, Sun L, Yang JY, Huelga SC, Hong WX, Zhang Q, Stout CD, Halpert JR Mol Pharmacol. 2010 Apr;77(4):529-38. Epub 2010 Jan 8. PMID:20061448^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Miyazawa M, Shindo M, Shimada T. Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica. 2001 Oct;31(10):713-23. PMID:11695850 doi:10.1080/00498250110065595
↑ Gay SC, Shah MB, Talakad JC, Maekawa K, Roberts AG, Wilderman PR, Sun L, Yang JY, Huelga SC, Hong WX, Zhang Q, Stout CD, Halpert JR. Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution. Mol Pharmacol. 2010 Apr;77(4):529-38. Epub 2010 Jan 8. PMID:20061448 doi:10.1124/mol.109.062570

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ibd"

@@ Line 3: / Line 3: @@
 <StructureSection load='3ibd' size='340' side='right'caption='[[3ibd]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ibd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IBD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ibd]] 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=3IBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IBD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2B6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3ibd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ibd OCA], [https://pdbe.org/3ibd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ibd RCSB], [https://www.ebi.ac.uk/pdbsum/3ibd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ibd ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Unspecific monooxygenase]]
+[[Category: Gay SC]]
-[[Category: Gay, S C]]
+[[Category: Halpert JR]]
-[[Category: Halpert, J R]]
+[[Category: Shah MB]]
-[[Category: Shah, M B]]
+[[Category: Stout DC]]
-[[Category: Stout, D C]]
+[[Category: Sun L]]
-[[Category: Sun, L]]
+[[Category: Talakad JC]]
-[[Category: Talakad, J C]]
-[[Category: Cyp 2b6]]
-[[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]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
-[[Category: P450]]
-[[Category: Phosphoprotein]]

3ibd

From Proteopedia

Current revision

Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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