9EF0

EM structure of cytochrome P450 reductase

9EF0 の概要

• エントリーDOI: 10.2210/pdb9ef0/pdb
• EMDBエントリー: 40857
• 分子名称: NADPH--cytochrome P450 reductase, FLAVIN MONONUCLEOTIDE, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: cytochrome p450 reductase, cpr, por, electron transfer, endoplasmic reticulum, flavoprotein, oxidoreductase
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 78299.66

構造登録者

Lepesheva, G.I.,Ren, Y. (登録日: 2024-11-19, 公開日: 2024-12-04, 最終更新日: 2026-02-04)

主引用文献

Lepesheva, G.I.,Hargrove, T.Y.,Ren, Y.
Cryo-EM reveals an ensemble of cytochrome P450 reductase conformations in solution.
Protein Sci., 35:e70448-e70448, 2026

PubMed Abstract: The eukaryotic electron transport system, mediated by cytochrome P450 reductase (CPR), plays a crucial role in driving myriads of reactions involved in the biosynthesis of physiologically active compounds (such as sterols, steroids, vitamins, and natural products), as well as in the metabolism of drugs, toxins, and carcinogens. CPR is a diflavin-containing enzyme found ubiquitously on the cytosolic side of the endoplasmic reticulum. While several crystal structures of CPR are available, its conformational states in solution, along with the molecular details of action, remain debatable. Here, we determined the 3.3 Å cryo-EM structure of rat CPR, marking the first electron microscopy structure of this relatively small protein (77 kDa). In this structure, the full-length, fully active enzyme adopts a compact conformation, which, however, is more relaxed than in crystal structures. Moreover, we structurally characterized less populated variations of compact CPR conformations and identified a fraction of molecules (~20%) with the FMN-binding domain either not visible or positioned far from the rest of the catalytic core. These results support the idea that large-scale interdomain rearrangements serve as the structural basis for CPR function and suggest that cryo-EM techniques can help uncover the intricate molecular mechanisms governing the CPR-mediated electron transfer cycle.

PubMed: 41562286
DOI: 10.1002/pro.70448

実験手法

ELECTRON MICROSCOPY (3.33 Å)