5em4

Structure of CYP2B4 F244W in a ligand free conformationStructure of CYP2B4 F244W in a ligand free conformation

Structural highlights 5em4 is a 2 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 3tmz, 2bdm, 1po5, 3uas, 3mvr, 2q6n, 3me6, 3kw4, 3tk3, 4h1n, 1suo, 3r1a, 3r1b, 3g93, 3g5n, 4jlt Gene: CYP2B4 (European rabbit) Activity: Unspecific monooxygenase, with EC number 1.14.14.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

spinqualitylabelsall models 5em4, resolution 3.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image