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| | ==Structure of CYP2B4 F244W in a ligand free conformation== | | ==Structure of CYP2B4 F244W in a ligand free conformation== |
| - | <StructureSection load='5em4' size='340' side='right' caption='[[5em4]], [[Resolution|resolution]] 3.02Å' scene=''> | + | <StructureSection load='5em4' size='340' side='right'caption='[[5em4]], [[Resolution|resolution]] 3.02Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5em4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EM4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EM4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5em4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EM4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 3.02Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tmz|3tmz]], [[2bdm|2bdm]], [[1po5|1po5]], [[3uas|3uas]], [[3mvr|3mvr]], [[2q6n|2q6n]], [[3me6|3me6]], [[3kw4|3kw4]], [[3tk3|3tk3]], [[4h1n|4h1n]], [[1suo|1suo]], [[3r1a|3r1a]], [[3r1b|3r1b]], [[3g93|3g93]], [[3g5n|3g5n]], [[4jlt|4jlt]]</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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</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=5em4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5em4 OCA], [https://pdbe.org/5em4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5em4 RCSB], [https://www.ebi.ac.uk/pdbsum/5em4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5em4 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=5em4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5em4 OCA], [http://pdbe.org/5em4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5em4 RCSB], [http://www.ebi.ac.uk/pdbsum/5em4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5em4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] 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 has a unique preference for the 5,6-olefin. | + | [https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT] 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 has a unique preference for the 5,6-olefin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5em4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5em4" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: European rabbit]] | + | [[Category: Large Structures]] |
| - | [[Category: Unspecific monooxygenase]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Halpert, J R]] | + | [[Category: Halpert JR]] |
| - | [[Category: Shah, M B]] | + | [[Category: Shah MB]] |
| - | [[Category: Stout, C D]] | + | [[Category: Stout CD]] |
| - | [[Category: Cytochrome p450]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
CP2B4_RABIT 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 has a unique preference for the 5,6-olefin.
Publication Abstract from PubMed
Using a combined structural and biochemical approach, the functional importance of a recently described peripheral pocket bounded by the E-, F-, G-, and I-helices in CYP2B4 and 2B6 was probed. Three series of 4-substituted-7-alkoxycoumarin derivatives with -H, -CH3, or -CF3 at the 4 position of the coumarin core were used initially to monitor functional differences between CYP2B4 and 2B6. 7-Ethoxy-4-(trifluoromethyl)coumarin (7-EFC) displayed the highest catalytic efficiency among these substrates. Mutants were made to alter side-chain polarity (V/E194Q) or bulk (F/Y244W) to alter access to the peripheral pocket. Modest increases in catalytic efficiency of 7-EFC O-deethylation by the mutants were magnified considerably by chlorination or bromination of the substrate ethoxy chain. A structure of CYP2B6 Y244W in complex with (+)-alpha-pinene was solved at 2.2 A and showed no CYMAL-5 in the peripheral pocket. A ligand free structure of CYP2B4 F244W was solved at 3.0 A with CYMAL-5 in the peripheral pocket. In both instances, comparison of the respective wild-type and mutant CYP2B enzymes revealed that CYMAL-5 occupancy of the peripheral pocket had little effect on the topology of active site residue side-chains, despite the fact that the peripheral pocket and active site are located on opposite sides of the I-helix. Analysis of available CYP2B structures suggest that the effect of the amino acid substitutions within the peripheral pocket derive from altered interactions between the F and G helices.
Coumarin Derivatives as Substrate Probes of Mammalian Cytochromes P450 2B4 and 2B6: Assessing the Importance of 7-Alkoxy Chain Length, Halogen Substitution, and Non-Active Site Mutations.,Liu J, Shah MB, Zhang Q, Stout CD, Halpert JR, Wilderman PR Biochemistry. 2016 Apr 5;55(13):1997-2007. doi: 10.1021/acs.biochem.5b01330. Epub, 2016 Mar 24. PMID:26982502[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu J, Shah MB, Zhang Q, Stout CD, Halpert JR, Wilderman PR. Coumarin Derivatives as Substrate Probes of Mammalian Cytochromes P450 2B4 and 2B6: Assessing the Importance of 7-Alkoxy Chain Length, Halogen Substitution, and Non-Active Site Mutations. Biochemistry. 2016 Apr 5;55(13):1997-2007. doi: 10.1021/acs.biochem.5b01330. Epub, 2016 Mar 24. PMID:26982502 doi:http://dx.doi.org/10.1021/acs.biochem.5b01330
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