Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism.
Cytochrome P450 2C9 (CYP2C9) is an important member of the cytochrome P450 enzyme superfamily with responsibility for metabolizing many important exogenous and endogenous compounds in many species of microorganisms, plants and animals. CYP2C9 is related to the oxidative of 16% of all therapeutics in current clinical use and has adverse drug effects, such as, enzyme induction and inhibition. In order to understand the metabolic mechanism of various drugs, two crystal structures of CYP2C9 have been studied, and their structural differences and structure-activity relationships with the drugs of Fluoxetine, Ibuprofen, Naproxen, Suprofen, and Mefenamic acid were investigated. By a series of docking studies and MD simulations, the binding pockets of CYP2C9 for the five drugs are explicitly defined that will be very useful for conducting mutagenesis studies, providing insights into the metabolic mechanism, which may be of relevance to the personalized drug.
Wang
Jing-Fang
JF
College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
Yan
Jing-Yi
JY
Wei
Dong-Qing
DQ
Chou
Kuo-Chen
KC
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D030562:Databases, Protein; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013499:Surface Properties
D008024:Ligands; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System