Recent Structural Insights into Cytochrome P450 Function

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• 作者：F. Peter Guengerich¹ ; ^{f.guengerich@vanderbilt.edu" class="auth_mail" title="E-mail the corresponding author} ; Michael R. Waterman¹ ; Martin Egli¹ ; ^{martin.egli@vanderbilt.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：cytochrome P450 ; drug metabolism ; steroid metabolism ; antibiotic discovery ; natural product biosynthesis
• 刊名：Trends in Pharmacological Sciences
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：37
• 期：8
• 页码：625-640
• 全文大小：4410 K

文摘

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.