3ES9

NADPH-Cytochrome P450 Reductase in an Open Conformation

3ES9 の概要

• エントリーDOI: 10.2210/pdb3es9/pdb
• 分子名称: NADPH--cytochrome P450 reductase, FLAVIN MONONUCLEOTIDE, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: cytochrome p450 reductase, oxidoreductase, open conformation, acetylation, endoplasmic reticulum, fad, flavoprotein, fmn, membrane, nadp, phosphoprotein
• 由来する生物種: Rattus norvegicus (rat)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein: P00388
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 215091.99

構造登録者

Hamdane, D.,Xia, C.,Im, S.-C.,Zhang, H.,Kim, J.-J.,Waskell, L. (登録日: 2008-10-05, 公開日: 2009-01-20, 最終更新日: 2023-09-06)

主引用文献

Hamdane, D.,Xia, C.,Im, S.C.,Zhang, H.,Kim, J.J.,Waskell, L.
Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450
J.Biol.Chem., 284:11374-11384, 2009

PubMed Abstract: NADPH-cytochrome P450 oxidoreductase (CYPOR) catalyzes the transfer of electrons to all known microsomal cytochromes P450. A CYPOR variant, with a 4-amino acid deletion in the hinge connecting the FMN domain to the rest of the protein, has been crystallized in three remarkably extended conformations. The variant donates an electron to cytochrome P450 at the same rate as the wild-type, when provided with sufficient electrons. Nevertheless, it is defective in its ability to transfer electrons intramolecularly from FAD to FMN. The three extended CYPOR structures demonstrate that, by pivoting on the C terminus of the hinge, the FMN domain of the enzyme undergoes a structural rearrangement that separates it from FAD and exposes the FMN, allowing it to interact with its redox partners. A similar movement most likely occurs in the wild-type enzyme in the course of transferring electrons from FAD to its physiological partner, cytochrome P450. A model of the complex between an open conformation of CYPOR and cytochrome P450 is presented that satisfies mutagenesis constraints. Neither lengthening the linker nor mutating its sequence influenced the activity of CYPOR. It is likely that the analogous linker in other members of the diflavin family functions in a similar manner.

PubMed: 19171935
DOI: 10.1074/jbc.M807868200

実験手法

X-RAY DIFFRACTION (3.4 Å)