2PG6

Crystal Structure of Human Microsomal P450 2A6 L240C/N297Q

2PG6 の概要

• エントリーDOI: 10.2210/pdb2pg6/pdb
• 関連するPDBエントリー: 1Z10 1Z11 2FDU 2FDV 2FDW 2FDY 2PG5 2PG7
• 分子名称: Cytochrome P450 2A6, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: cyp2a6, p450 2a6, p450, monooxygenases, drug metabolizing enzyme, heme, indole, mutant, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein: P11509
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 221168.54

構造登録者

Sansen, S.,Hsu, M.H.,Stout, C.D.,Johnson, E.F. (登録日: 2007-04-06, 公開日: 2007-07-24, 最終更新日: 2023-08-30)

主引用文献

Sansen, S.,Hsu, M.H.,Stout, C.D.,Johnson, E.F.
Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants.
Arch.Biochem.Biophys., 464:197-206, 2007

PubMed Abstract: Human P450 2A6 displays a small active site that is well adapted for the oxidation of small planar substrates. Mutagenesis of CYP2A6 resulted in an increased catalytic efficiency for indole biotransformation to pigments and conferred a capacity to oxidize substituted indoles (Wu, Z.-L., Podust, L.M., Guengerich, F.P. J. Biol. Chem. 49 (2005) 41090-41100.). Here, we describe the structural basis that underlies the altered metabolic profile of three mutant enzymes, P450 2A6 N297Q, L240C/N297Q and N297Q/I300V. The Asn297 substitution abolishes a potential hydrogen bonding interaction with substrates in the active site, and replaces a structural water molecule between the helix B'-C region and helix I while maintaining structural hydrogen bonding interactions. The structures of the P450 2A6 N297Q/L240C and N297Q/I300V mutants provide clues as to how the protein can adapt to fit the larger substituted indoles in the active site, and enable a comparison with other P450 family 2 enzymes for which the residue at the equivalent position was seen to function in isozyme specificity, structural integrity and protein flexibility.

PubMed: 17540336
DOI: 10.1016/j.abb.2007.04.028

実験手法

X-RAY DIFFRACTION (2.53 Å)