Kandel Sylvie E, Lampe Jed N
XenoTech, LLC , 16825 West 116th Street, Lenexa, Kansas 66219, United States.
Chem Res Toxicol. 2014 Sep 15;27(9):1474-86. doi: 10.1021/tx500203s. Epub 2014 Aug 29.
Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein-protein interactions play a critical role in this process. Historically, the study of CYP-protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein-protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein-protein interactions with CYP enzymes.
细胞色素P450单加氧酶（CYPs）通过其独特的氧化化学作用，催化人体中大多数药物和毒素的清除。蛋白质-蛋白质相互作用在这一过程中起着关键作用。从历史上看，对CYP-蛋白质相互作用的研究主要集中在其电子传递伙伴和变构介质，即细胞色素P450还原酶和细胞色素b5。然而，CYPs可以结合其他也会影响CYP功能的蛋白质。除了其他CYP同工型外，一些例子包括孕激素受体膜成分1、抗损伤蛋白1、人血清白蛋白和牛血清白蛋白以及肠道脂肪酸结合蛋白。此外，这些相互作用的破坏可能导致代谢途径改变和有毒代谢产物的产生。在这篇综述中，我们总结了文献中关于CYP蛋白质-蛋白质相互作用的现有证据，并讨论了未来旨在表征与CYP酶的非经典蛋白质-蛋白质相互作用的研究的潜在影响。
