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.
Cytochrome CYP2C9 binding pockets Structureactivity relationship metabolic mechanism
Jing-Yi Yan Jing-Fang Wang Dong-Qing Wei
Department of Chemistry and Chemical Engineering Shanghai Jiaotong Univeristy Shanghai, 200240, Chin Bioinformatics Center, Key Lab of Systems Biology Shanghai Institutes for Biological Sciences, Chine Department of Bioinformatics and Biostatistics, College of Life Science and Biotechnology Shanghai J
国际会议
上海
英文
163-166
2008-05-16（万方平台首次上网日期，不代表论文的发表时间）