5UFG

Crystal Structure of CYP2B6 (Y226H/K262R/I114V) in complex with myrtenyl bromide

Summary for 5UFG

• Entry DOI: 10.2210/pdb5ufg/pdb
• Related: 3IBD 4I91 5UAP 5UDA 5UEC
• Descriptor: Cytochrome P450 2B6, PROTOPORPHYRIN IX CONTAINING FE, 5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE, ... (5 entities in total)
• Functional Keywords: oxidoreductase, cytochrome p450 2b6
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 56947.32

Authors

Shah, M.B.,Halpert, J.R. (deposition date: 2017-01-04, release date: 2017-04-12, Last modification date: 2023-10-04)

Primary citation

Shah, M.B.,Liu, J.,Zhang, Q.,Stout, C.D.,Halpert, J.R.
Halogen-pi Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.
ACS Chem. Biol., 12:1204-1210, 2017

PubMed Abstract: Numerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen-π 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-π 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 Å compared with the latter complex. The bromine in myrtenyl bromide π-bonded with Phe297 in CYP2B6, whereas the two major orientations in the active site mutant I114V exhibited bromine-π interactions with two additional residues, Phe108 and Phe115. Analysis of existing structures suggests that halogen-π interactions may be unique to the CYP2B enzymes within CYP family 2 but are also important for CYP3A enzymes.

PubMed: 28368100
DOI: 10.1021/acschembio.7b00056

Experimental method

X-RAY DIFFRACTION (1.76 Å)