4jlt

Crystal structure of P450 2B4(H226Y) in complex with paroxetine

spinqualitylabelsall models 4jlt, resolution 2.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jlt is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 8PR, CM5, GOL, HEM, PO4, SO4 Related: 2q6n, 3kw4, 2bdm, 1suo, 3me6, 3mvr, 3g5n, 3r1a, 3r1b, 3g93, 1po5, 3uas, 4h1n, 3tk3, 3tmz Gene: CYP2B4 (Oryctolagus cuniculus) Activity: Unspecific monooxygenase, with EC number 1.14.14.1 Resources: FirstGlance, OCA, 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. Publication Abstract from PubMed An X-ray crystal structure of CYP2B4 in complex with the drug paroxetine [(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine] was solved at 2.14 A resolution. The structure revealed a conformation intermediate to that of the recently solved complex with amlodipine and that of the more compact complex with 4-(4-chlorophenyl)imidazole in terms of the placement of the F-G cassette. Moreover, comparison of the new structure with 15 previously solved structures of CYP2B4 revealed some new insights into the determinants of active-site size and shape. The 2B4-paroxetine structure is nearly superimposable on a previously solved closed structure in a ligand-free state. Despite the overall conformational similarity among multiple closed structures, the active-site cavity volume of the paroxetine complex is enlarged. Further analysis of the accessible space and binding pocket near the heme reveals a new subchamber that resulted from the movement of secondary structural elements and rearrangements of active-site side chains. Overall, the results from the comparison of all 16 structures of CYP2B4 demonstrate a cluster of protein conformations that were observed in the presence or absence of various ligands. A Structural Snapshot of CYP2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States.,Shah MB, Kufareva I, Pascual J, Zhang Q, Stout CD, Halpert JR J Pharmacol Exp Ther. 2013 Jul;346(1):113-20. doi: 10.1124/jpet.113.204776. Epub , 2013 Apr 30. PMID:23633618 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450

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