3D structure modeling of cytochrome P450 2C19 and its implication for personalized drug design

Jing Fang Wang; Dong Qing Wei; Lin Li; Si Yuan Zheng; Yi Xue Li; Kuo Chen Chou

doi:10.1016/j.bbrc.2007.01.185

3D structure modeling of cytochrome P450 2C19 and its implication for personalized drug design

Jing Fang Wang, Dong Qing Wei, Lin Li, Si Yuan Zheng, Yi Xue Li, Kuo Chen Chou

Bioinformatics & Computational Biology

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

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.

Original language	English (US)
Pages (from-to)	513-519
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	355
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2007.01.185
State	Published - Apr 6 2007

Keywords

CEC
CYP2C19
Cytochrome P-450
Fluvoxamine
Lescol
Personalized drug design
Structure-activity relationship
Ticlopidine

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2007.01.185

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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.",

keywords = "CEC, CYP2C19, Cytochrome P-450, Fluvoxamine, Lescol, Personalized drug design, Structure-activity relationship, Ticlopidine",

author = "Wang, {Jing Fang} and Wei, {Dong Qing} and Lin Li and Zheng, {Si Yuan} and Li, {Yi Xue} and Chou, {Kuo Chen}",

note = "Funding Information: Valuable discussions with Professor Chen Chao of Chinese National Engineering Center on Micro-measurement and Professor Li Rulin of North West University are gratefully acknowledged. This work was supported by the grants from Chinese National Science Foundation under the Contract No.10376024, the Tianjin Commission of Education under contract No. 20030001 and the Tianjin Commission of Sciences and Technology under the Contract No. 033801911. Additional supports were from the special fund for intensive computation, Virtual Laboratory for Computational Chemistry of CNIC, and the Supercomputing Center of CNIC, Chinese Academy of Sciences under the contract No. 043185111-4.",

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AU - Li, Yi Xue

AU - Chou, Kuo Chen

N1 - Funding Information: Valuable discussions with Professor Chen Chao of Chinese National Engineering Center on Micro-measurement and Professor Li Rulin of North West University are gratefully acknowledged. This work was supported by the grants from Chinese National Science Foundation under the Contract No.10376024, the Tianjin Commission of Education under contract No. 20030001 and the Tianjin Commission of Sciences and Technology under the Contract No. 033801911. Additional supports were from the special fund for intensive computation, Virtual Laboratory for Computational Chemistry of CNIC, and the Supercomputing Center of CNIC, Chinese Academy of Sciences under the contract No. 043185111-4.

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N2 - 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.

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3D structure modeling of cytochrome P450 2C19 and its implication for personalized drug design

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