Wang Jing-Fang, Wei Dong-Qing, Li Lin, Zheng Si-Yuan, Li Yi-Xue, Chou Kuo-Chen
College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China.
Biochem Biophys Res Commun. 2007 Apr 6;355(2):513-9. doi: 10.1016/j.bbrc.2007.01.185. Epub 2007 Feb 8.
Cytochrome P450 2C19 (CYP2C19) is a member of the cytochrome P-450 enzyme superfamily and plays an important role in the metabolism of drugs. In order to gain insights for developing personalized drugs, the 3D (dimensional) structure of CYP2C19 has been developed based on the crystal structure of CYP2C9 (PDB code 1R90), and its structure-activity relationship with the ligands of CEC, Fluvoxamine, Lescol, and Ticlopidine investigated through the structure-activity relationship approach. By means of a series of docking studies, the binding pockets of CYP2C19 for the four compounds are explicitly defined that will be very useful for conducting mutagenesis studies, providing insights into personalization of drug treatments and stimulating novel strategies for finding desired personalized drugs.
细胞色素P450 2C19（CYP2C19）是细胞色素P - 450酶超家族的成员，在药物代谢中起重要作用。为了获得开发个性化药物的见解，基于细胞色素P450 2C9的晶体结构（蛋白质数据银行代码1R90）构建了CYP2C19的三维结构，并通过构效关系方法研究了它与西酞普兰、氟伏沙明、来适可和噻氯匹定配体的构效关系。通过一系列对接研究，明确确定了CYP2C19对这四种化合物的结合口袋，这对于进行诱变研究、深入了解药物治疗的个性化以及激发寻找所需个性化药物的新策略将非常有用。
