Recent Structural Insights into Cytochrome P450 Function.
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.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. Electronic address: f.guengerich@vanderbilt.edu.
F Peter
FP
Guengerich
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Michael R
MR
Waterman
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. Electronic address: martin.egli@vanderbilt.edu.
Martin
M
Egli
D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System
antibiotic discovery; cytochrome P450; drug metabolism; natural product biosynthesis; steroid metabolism