| Project/Area Number |
24590366
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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 |
General medical chemistry
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| Research Institution | Teikyo University (2014)
Kurume University (2012-2013) |
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Principal Investigator |
NOGUCHI Masato 帝京大学, 帝京大学福岡医療技術学部, 教授 (10124611)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Hideaki 久留米大学, 医学部, 准教授 (60271996)
SUGISHIMA Masakazu 久留米大学, 医学部, 准教授 (30379292)
HIGASHIMOTO Yuichiro 久留米大学, 医学部, 准教授 (40352124)
HARADA Jiro 久留米大学, 医学部, 講師 (10373039)
原田 二朗 久留米大学, 医学部, 講師 (10373094)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 生理的ヘム分解 / ヘムオキシゲナーゼ / シトクロムP450還元酵素 / 蛋白質間の電子伝達 / 酸素分子の活性化 / ビリルビン / ビリベルジン / シトクロムp450還元酵素 / ヘムオキシゲナ－ゼ / タンパク質間の電子伝達 / 一酸化炭素 |
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| Outline of Final Research Achievements |
NADPH-cytochrome P450 oxidoreductase (CPR) supplies electrons to various heme proteins including heme oxygenase (HO), which is a key enzyme for heme degradation. Electrons from NADPH flow first to FAD then to FMN, and finally to heme in the redox partner. For electron transfer from CPR to its redox partner, the ‘‘closed-open transition’’ of CPR is indispensable. Here, we demonstrate that a hinge-shortened CPR variant, which favors an open conformation, makes a stable complex with heme-HO-1 and can support the HO reaction, though its efficiency is extremely limited. Furthermore, we determined the crystal structure of the CPR variant in complex with heme-HO-1 at 4.3A; resolution. This is the first time the crystal structure of a complex of CPR and its redox partner has been characterized. The distance between heme and FMN in this complex (6A) implies the direct electron transfer from FMN to heme.
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