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| | ==Structure of Cytochrome P450 2B4 with Bound Bifonazole== | | ==Structure of Cytochrome P450 2B4 with Bound Bifonazole== |
| - | <StructureSection load='2bdm' size='340' side='right' caption='[[2bdm]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='2bdm' size='340' side='right'caption='[[2bdm]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bdm]] is a 1 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=2BDM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BDM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bdm]] is a 1 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=2BDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BDM 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>, <scene name='pdbligand=TMI:1-[PHENYL-(4-PHENYLPHENYL)-METHYL]IMIDAZOLE'>TMI</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1suo|1suo]], [[1po5|1po5]]</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>, <scene name='pdbligand=TMI:1-[PHENYL-(4-PHENYLPHENYL)-METHYL]IMIDAZOLE'>TMI</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=2bdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bdm OCA], [https://pdbe.org/2bdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bdm RCSB], [https://www.ebi.ac.uk/pdbsum/2bdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bdm 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=2bdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bdm OCA], [http://pdbe.org/2bdm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bdm RCSB], [http://www.ebi.ac.uk/pdbsum/2bdm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bdm 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bd/2bdm_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bd/2bdm_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2bdm" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2bdm" 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: Muralidhara, B K]] | + | [[Category: Muralidhara BK]] |
| - | [[Category: Stout, C D]] | + | [[Category: Stout CD]] |
| - | [[Category: Sun, L]] | + | [[Category: Sun L]] |
| - | [[Category: White, M A]] | + | [[Category: White MA]] |
| - | [[Category: Zhao, Y]] | + | [[Category: Zhao Y]] |
| - | [[Category: Cyp 2b4]]
| + | |
| - | [[Category: Cyp lm2]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: P450]]
| + | |
| 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.
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
To better understand ligand-induced structural transitions in cytochrome P450 2B4, protein-ligand interactions were investigated using a bulky inhibitor. Bifonazole, a broad spectrum antifungal agent, inhibits monooxygenase activity and induces a type II binding spectrum in 2B4dH(H226Y), a modified enzyme previously crystallized in the presence of 4-(4-chlorophenyl)imidazole (CPI). Isothermal titration calorimetry and tryptophan fluorescence quenching indicate no significant burial of protein apolar surface nor altered accessibility of Trp-121 upon bifonazole binding, in contrast to recent results with CPI. A 2.3 A crystal structure of 2B4-bifonazole reveals a novel open conformation with ligand bound in the active site, which is significantly different from either the U-shaped cleft of ligand-free 2B4 or the small active site pocket of 2B4-CPI. The O-shaped active site cleft of 2B4-bifonazole is widely open in the middle but narrow at the top. A bifonazole molecule occupies the bottom of the active site cleft, where helix I is bent approximately 15 degrees to accommodate the bulky ligand. The structure also defines unanticipated interactions between helix C residues and bifonazole, suggesting an important role of helix C in azole recognition by mammalian P450s. Comparison of the ligand-free 2B4 structure, the 2B4-CPI structure, and the 2B4-bifonazole structure identifies structurally plastic regions that undergo correlated conformational changes in response to ligand binding. The most plastic regions are putative membrane-binding motifs involved in substrate access or substrate binding. The results allow us to model the membrane-associated state of P450 and provide insight into how lipophilic substrates access the buried active site.
Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction.,Zhao Y, White MA, Muralidhara BK, Sun L, Halpert JR, Stout CD J Biol Chem. 2006 Mar 3;281(9):5973-81. Epub 2005 Dec 21. PMID:16373351[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhao Y, White MA, Muralidhara BK, Sun L, Halpert JR, Stout CD. Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction. J Biol Chem. 2006 Mar 3;281(9):5973-81. Epub 2005 Dec 21. PMID:16373351 doi:10.1074/jbc.M511464200
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