| Project/Area Number |
26460038
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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 |
Physical pharmacy
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高橋 栄夫 横浜市立大学, 生命医科学研究科, 教授 (60265717)
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| Research Collaborator |
FUJII Moe 横浜市立大学, 大学院生命医科学研究科, 技術補助員
FUSHIMI Taketoshi 横浜市立大学, 大学院生命医科学研究科, 大学院生
KOIKE Kenichiro 横浜市立大学, 大学院生命医科学研究科, 大学院生
SUZUKI Rika 横浜市立大学, 大学院生命医科学研究科, 大学院生
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 構造生物学 |
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| Outline of Final Research Achievements |
Eicosanoids are chemical mediators synthesized from arachidonic acid. Three tetra-span trimeric membrane proteins, FLAP, LTC4S, and mPGES1, are (co)-enzymes involved in this arachidonic acid metabolism, and are thought to be drug targets. To understand molecular mechanisms for these proteins to function, we performed structural analyses of these membrane proteins using NMR. We expressed these proteins by using the yeast Pichia pastoris expression system, and found the yield of FLAP is more than 30 times higher than that of the E. coli system. We then reconstituted these proteins in detergent micelles and/or nanolipoprotein particles. The NMR interaction study of FLAP and its inhibitor MK-591 revealed that amino acids located more than 10 angstrom apart from the ligand in the crystal structure experienced chemical shift change by the addition of the inhibitor, which suggests the MK-591 binding induces conformational changes around the transmembrane helices of FLAP.
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