2bdm
From Proteopedia
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|PDB= 2bdm |SIZE=350|CAPTION= <scene name='initialview01'>2bdm</scene>, resolution 2.300Å | |PDB= 2bdm |SIZE=350|CAPTION= <scene name='initialview01'>2bdm</scene>, resolution 2.300Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TMI:1-[PHENYL-(4-PHENYLPHENYL)-METHYL]IMIDAZOLE'>TMI</scene> | + | |LIGAND= <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> |
| - | + | |ACTIVITY= <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> | |
|GENE= CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | |GENE= CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1suo|1SUO]], [[1po5|1PO5]] | ||
| + | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/2bdm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bdm RCSB]</span> | ||
}} | }} | ||
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[[Category: White, M A.]] | [[Category: White, M A.]] | ||
[[Category: Zhao, Y.]] | [[Category: Zhao, Y.]] | ||
| - | [[Category: CM5]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: TMI]] | ||
[[Category: cyp 2b4]] | [[Category: cyp 2b4]] | ||
[[Category: cyp lm2]] | [[Category: cyp lm2]] | ||
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[[Category: p450]] | [[Category: p450]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:04:52 2008'' |
Revision as of 23:04, 30 March 2008
| |||||||
| , resolution 2.300Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | CYP2B4 (Oryctolagus cuniculus) | ||||||
| Activity: | Unspecific monooxygenase, with EC number 1.14.14.1 | ||||||
| Related: | 1SUO, 1PO5
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Cytochrome P450 2B4 with Bound Bifonazole
Overview
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.
About this Structure
2BDM is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
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
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