5UDA

Crystal structure of CYP2B6 (Y226H/K262R) in complex with a monoterpene bornane

5UDA の概要

• エントリーDOI: 10.2210/pdb5uda/pdb
• 関連するPDBエントリー: 5UEC
• 分子名称: Cytochrome P450 2B6, PROTOPORPHYRIN IX CONTAINING FE, CAMPHANE, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, cytochrome p450, cyp2b6
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 113768.92

構造登録者

Shah, M.B.,Halpert, J.R. (登録日: 2016-12-24, 公開日: 2017-04-12, 最終更新日: 2023-10-04)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.93 Å)