2F9Q

Crystal Structure of Human Cytochrome P450 2D6

2F9Q の概要

• エントリーDOI: 10.2210/pdb2f9q/pdb
• 分子名称: Cytochrome P450 2D6, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: cytochrome p450 2d6; haem, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein: P10635
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 217892.47

構造登録者

Rowland, P. (登録日: 2005-12-06, 公開日: 2005-12-20, 最終更新日: 2024-02-14)

主引用文献

Rowland, P.,Blaney, F.E.,Smyth, M.G.,Jones, J.J.,Leydon, V.R.,Oxbrow, A.K.,Lewis, C.J.,Tennant, M.G.,Modi, S.,Eggleston, D.S.,Chenery, R.J.,Bridges, A.M.
Crystal Structure of Human Cytochrome P450 2D6
J.Biol.Chem., 281:7614-7622, 2006

PubMed Abstract: Cytochrome P450 2D6 is a heme-containing enzyme that is responsible for the metabolism of at least 20% of known drugs. Substrates of 2D6 typically contain a basic nitrogen and a planar aromatic ring. The crystal structure of human 2D6 has been solved and refined to 3.0A resolution. The structure shows the characteristic P450 fold as seen in other members of the family, with the lengths and orientations of the individual secondary structural elements being very similar to those seen in 2C9. There are, however, several important differences, the most notable involving the F helix, the F-G loop, the B'helix, beta sheet 4, and part of beta sheet 1, all of which are situated on the distal face of the protein. The 2D6 structure has a well defined active site cavity above the heme group, containing many important residues that have been implicated in substrate recognition and binding, including Asp-301, Glu-216, Phe-483, and Phe-120. The crystal structure helps to explain how Asp-301, Glu-216, and Phe-483 can act as substrate binding residues and suggests that the role of Phe-120 is to control the orientation of the aromatic ring found in most substrates with respect to the heme. The structure has been compared with published homology models and has been used to explain much of the reported site-directed mutagenesis data and help understand the metabolism of several compounds.

PubMed: 16352597
DOI: 10.1074/jbc.M511232200

実験手法

X-RAY DIFFRACTION (3.002 Å)