Structural highlights
3g5n is a 4 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | 2q6n, 1suo, 2bdm, 1po5 |
| Gene: | CYP2B4 (European rabbit) |
| Activity: | Unspecific monooxygenase, with EC number 1.14.14.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
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
Two different ligand occupancy structures of cytochrome P450 2B4 (CYP2B4) in complex with 1-biphenyl-4-methyl-1H-imidazole (1-PBI) have been solved by x-ray crystallography. 1-PBI belongs to a series of tight binding, imidazole-based CYP2B4 inhibitors. 1-PBI binding to CYP2B4 yields a type II spectrum with a Ks value of 0.23 microM and inhibits enzyme activity with an IC50 value of 0.035 microM. Previous CYP2B4 structures have shown a large degree of structural movement in response to ligand size. With two phenyl rings, 1-PBI is larger than 1-(4-chlorophenyl)imidazole (1-CPI) and 4-(4-chlorophenyl)imidazole (4-CPI) but smaller than bifonazole, which is branched and contains three phenyl rings. The CYP2B4:1-PBI complex is a structural intermediate to the closed CPI and the open bifonazole structures. The B/C loop reorganizes itself to include two short partial helices while closing one side of the active site. The F-G helix cassette pivots over the I-helix in direct response to the size of the ligand in the active site. A cluster of Phe residues at the fulcrum of this pivot point allows for dramatic repositioning of the cassette with only a relatively small amount of secondary structure rearrangement. Comparisons of ligand bound CYP2B4 structures reveal trends in plastic region mobility that could allow for predictions of their position in future structures based on ligand shape and size.
Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1-biphenyl-4-methyl-1Himidazole: ligand induced structural response through -helical repositioning.,Gay SC, Sun L, Maekawa K, Halpert JR, Stout CD Biochemistry. 2009 Apr 27. PMID:19397311[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gay SC, Sun L, Maekawa K, Halpert JR, Stout CD. Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1-biphenyl-4-methyl-1Himidazole: ligand induced structural response through -helical repositioning. Biochemistry. 2009 Apr 27. PMID:19397311 doi:10.1021/bi9003765
