title: 3D structure modeling of cytochrome P450 2C19 and its implication for personalized drug design.
abstract: 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.
authors.affiliation: College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Jing-Fang
authors.initials: JF
authors.lastname: Wang
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zheng
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Li
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Chou
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry* / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D015195:Drug Design; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D000077340:Fluvastatin; D016666:Fluvoxamine / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008024:Ligands; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009570:Nitriles / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013988:Ticlopidine / Q000378:metabolism
chemical_list: D003374:Coumarins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008024:Ligands; D009570:Nitriles; C057714:3-cyano-7-ethoxycoumarin; D000077340:Fluvastatin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D016666:Fluvoxamine; D013988:Ticlopidine