| Project/Area Number |
26440081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
古田 忠臣 東京工業大学, 生命理工学院, 助教 (10431834)
岡本 研 日本医科大学, 医学部, 准教授 (60267143)
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| Co-Investigator(Renkei-kenkyūsha) |
FUJISAKI Hiroshi 日本医科大学, 医学部, 准教授 (60573243)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 酸化還元酵素 / 構造・機能予測 / 分子動力学 / キサンチン / 痛風治療薬 / 阻害剤 / フェブキソスタット / BOF / 創薬 |
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| Outline of Final Research Achievements |
Xanthine oxidoreductase (XOR) physiologically catalyzes the hydroxylation of hypoxanthine to xanthine, followed by the catalysis of the hydroxylation of xanthine to uric acid. As excess production of uric acid leads to gout, human XOR has been a target of anti-gout drugs. XOR is found in a wide range of organisms from bacteria to human, and the substrate-binding pockets of mammalian and bacterial XOR are well-conserved as regards catalytically important residues and three-dimensional structure. In this research, we found in terms of enzymatic experiments that inhibitor BOF-4272 (BOF) inhibits mammalian XOR but not bacterial XOR. This means that it is difficult to understand the inhibitory mechanism of BOF from the view point of only the static three-dimensional structure of XOR. However, we succeeded in reproducing the experiment results using MD calculations from the view point of dynamics.
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