Interactions of CYP2C9 with Different Substrates and its Implications for Metabolic Mechanism

Cytochrome P450 2C9 (CYP2C9) is among most important members of the cytochrome P450 enzyme superfamily, which metabolizes 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 clinical use and has adverse drug effects, for example, enzyme induction and inhibition. In order to understand the metabolic mechanism of various drugs, two crystal structures of CYP2C9 have been studied, and their structure-activity relationships with the drugs of Fluoxetine, Ibuprofen, Naproxen, Suprofen, and Mefenamic acid investigated. By 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 of relevance to the personalized drug.