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Crystal Structure of CYP2B6 (Y226H/K262R/I114V) in complex with myrtenyl bromide
Structural highlights
FunctionCP2B6_HUMAN 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. Acts as a 1,4-cineole 2-exo-monooxygenase.[1] Publication Abstract from PubMedNumerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen-pi bonds in substrate selectivity and orientation in the active site, structures of four CYP2B6 monoterpenoid complexes were solved by X-ray crystallography. Bornyl bromide exhibited dual orientations in the active site with the predominant orientation revealing a bromine-pi bond with the Phe108 side chain. Bornane demonstrated two orientations with equal occupancy; in both, the C2 atom that bears the bromine in bornyl bromide was displaced by more than 2.5 A compared with the latter complex. The bromine in myrtenyl bromide pi-bonded with Phe297 in CYP2B6, whereas the two major orientations in the active site mutant I114V exhibited bromine-pi interactions with two additional residues, Phe108 and Phe115. Analysis of existing structures suggests that halogen-pi interactions may be unique to the CYP2B enzymes within CYP family 2 but are also important for CYP3A enzymes. Halogen-pi Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.,Shah MB, Liu J, Zhang Q, Stout CD, Halpert JR ACS Chem Biol. 2017 Apr 6. doi: 10.1021/acschembio.7b00056. PMID:28368100[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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