Guengerich F Peter, Waterman Michael R, Egli Martin
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Trends Pharmacol Sci. 2016 Aug;37(8):625-640. doi: 10.1016/j.tips.2016.05.006. Epub 2016 Jun 4.
Cytochrome P450 (P450) enzymes are important in the metabolism of drugs, steroids, fat-soluble vitamins, carcinogens, pesticides, and many other types of chemicals. Their catalytic activities are important issues in areas such as drug-drug interactions and endocrine function. During the past 30 years, structures of P450s have been very helpful in understanding function, particularly the mammalian P450 structures available in the past 15 years. We review recent activity in this area, focusing on the past 2 years (2014-2015). Structural work with microbial P450s includes studies related to the biosynthesis of natural products and the use of parasitic and fungal P450 structures as targets for drug discovery. Studies on mammalian P450s include the utilization of information about 'drug-metabolizing' P450s to improve drug development and also to understand the molecular bases of endocrine dysfunction.
细胞色素P450(P450)酶在药物、类固醇、脂溶性维生素、致癌物、杀虫剂及许多其他类型化学物质的代谢过程中发挥着重要作用。它们的催化活性在诸如药物相互作用和内分泌功能等领域是重要问题。在过去30年里,P450的结构对于理解其功能非常有帮助,尤其是过去15年中已获得的哺乳动物P450结构。我们回顾了该领域的近期研究进展,重点关注过去两年(2014 - 2015年)。微生物P450的结构研究包括与天然产物生物合成相关的研究,以及将寄生和真菌P450结构用作药物发现靶点的研究。对哺乳动物P450的研究包括利用“药物代谢”P450的信息来改进药物开发,以及理解内分泌功能障碍的分子基础。