2016 Fiscal Year Final Research Report
The gout medicine which has strong effects on mammalian XOR but not on bacterial XOR: dynamics of the interaction between enzyme XOR and its inhibitor BOF
| Project/Area Number |
26440081
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Biophysics
|
|---|
| Research Institution | Nippon Medical School |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
FUJISAKI Hiroshi 日本医科大学, 医学部, 准教授 (60573243)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| 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 |
|---|
| 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.
|
| Free Research Field |
生物物理学
|
