Halogen-π Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.

摘要: Numerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen−π bonds in substrate selectivity orientation active site, structures four CYP2B6 monoterpenoid complexes were solved by X-ray crystallography. Bornyl bromide exhibited dual orientations site with predominant revealing a bromine−π bond Phe108 side chain. Bornane demonstrated two equal occupancy; both, C2 atom that bears bromine bornyl was displaced more than 2.5 A compared latter complex. The myrtenyl π-bonded Phe297 CYP2B6, whereas major mutant I114V interactions additional residues, Phe115. Analysis existing suggests may be unique to CYP2B enzymes within CYP family 2 but also important for CYP3A enzymes.