Characterization of the CYP3A4 Active Site by Homology Modeling
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概要
- 論文の詳細を見る
Human microsomal cytochrome P450s participate in drug metabolism and detoxification. Among them, CYP3A4 is the most important isoform for drug-drug interactions. To gain a better understanding of the active site, a homology model of CYP3A4 was constructed based on the crystallographic coordinates of mammalian CYP2C5. The putative active site is much larger than that of CYP2C5 and is divided into three parts (i.e. a proximal and two distal sites from the heme). Most residues reported to be important for ligand-binding are located in the active site of the model. Moreover, some inhibitors (paclitaxel etc.) docked into the model have complementary shapes to the pocket. Pharmacophore docking of 14 substrates was also performed using Ph4Dock of MOE. Calculated interaction energies showed a moderate correlation with the logarithm of apparent K_m values. These results suggest that this model is reliable enough to be used in the design of compounds for removing undesirable CYP3A4 inhibition.
- 公益社団法人日本薬学会の論文
- 2004-07-01
著者
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山城 祐子
Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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Tanaka Toshimasa
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
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山本 譲
Faculty Of Pharmaceutical Sciences Kanazawa University
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Tanaka T
Kvushu Univ. Fukuoka Jpn
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Tanaka T
Osaka Univ. Osaka Jpn
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Tanaka Toshimasa
Pharmaceutical Research Division Discovery Research Center Takeda Pharmaceutical Company Limited
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Yamamoto Y
Tohoku Univ. Sendai Jpn
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田中 恒雄
Department Of Pharmacy Hyogo College Of Medicine
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Yamamoto Y
Pharmaceutical Research Laboratory Hokuriku Seiyaku Co. Ltd.
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Yamamoto Y
School Of Pharmaceutical Sciences Toho University
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Tanaka Tetsuaki
Faculty Of Pharmaceutical Sciences Osaka University
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OKUDA Teruaki
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
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YAMAMOTO Yoshio
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
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Yamamoto Yoshio
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
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Okuda T
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
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Tanaka T
School Of Pharmaceutical Sciences Nagasaki University
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Yamamoto Y
大阪薬科大学
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Okuda Teruaki
Faculty Of Pharmaceutical Sciences Osaka University
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山本 靖夫
School Of Pharmaceutical Sciences Toho University
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Tanaka Terumichi
Division Of Bioscience And Biotechnology Department Of Ecological Engineering Toyohashi University O
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