Xia Songyan, Hirao Hajime
Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.
Molecules. 2025 Sep 13;30(18):3733. doi: 10.3390/molecules30183733.
NADPH-cytochrome P450 reductase (CPR) is an essential redox partner for a wide range of metal-containing proteins, mediating the stepwise transfer of two electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to the redox centers of its partner proteins. This Perspective summarizes recent advances in understanding the mechanisms underlying the CPR-mediated electron transfer (ET) cycle. Emphasis is placed on human and other mammalian CPRs, which provide critical insights into human biology and drug metabolism. Recent experimental and computational approaches that have deepened our mechanistic understanding of CPR function are highlighted. Selected studies are reviewed to illustrate progress in elucidating the interflavin ET within CPR, the interplay between its redox states and structural dynamics, and its protein-protein interactions with redox partners, along with the associated ET pathways. Finally, the remaining challenges and future research directions are outlined.
烟酰胺腺嘌呤二核苷酸磷酸细胞色素P450还原酶（CPR）是多种含金属蛋白必不可少的氧化还原伙伴，介导两个电子从烟酰胺腺嘌呤二核苷酸磷酸（NADPH）逐步转移至其伙伴蛋白的氧化还原中心。本综述总结了在理解CPR介导的电子转移（ET）循环机制方面的最新进展。重点关注人类及其他哺乳动物的CPR，它们为人类生物学和药物代谢提供了关键见解。文中突出了近期深化我们对CPR功能机制理解的实验和计算方法。回顾了部分研究，以阐明CPR内黄素间电子转移、其氧化还原状态与结构动力学之间的相互作用、与氧化还原伙伴的蛋白质-蛋白质相互作用以及相关的电子转移途径方面取得的进展。最后，概述了剩余的挑战和未来的研究方向。
