Structural and functional relationship of aqauporin-4 in brain
| Project/Area Number |
26440024
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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 |
Structural biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
Tani Kazutoshi 名古屋大学, 細胞生理学研究センター, 特任教授 (20541204)
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| Co-Investigator(Renkei-kenkyūsha) |
Fujiyoshi Yoshinori 名古屋大学, 細胞生理学研究センター, 特任教授 (80142298)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 構造生理学 / 電子線結晶学 / 二次元結晶 / アクアポリン-4 / 極低温電子顕微鏡 / 水透過機構 |
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| Outline of Final Research Achievements |
To reveal the inhibition mechanisms of water channel aquaporin-4 (AQP4), we determined the AQP4 structures in complex with mercury or acetazolamide, an ihnibitor of dehydrogenase, using cryo-electron microscopy. The binding sites of mercury and AZA were found at the cytoplasmic and the extracelluar side, respectively. In the mercury bound AQP4 structure, the binding sites were not determined at atomic level, but mercury binding could not invoke the large conformational change of the loop D of AQP4 including the binding site of Cys178. The AZA bound AQP4 revealed the AZA binding site to block water pathway near the channel entrance at the extracelluar side, but we could not model the conformation of AZA due to the ambiguous density corrsponding to the binding site. Further improvement of the crystal quality of AZA bound AQP4 is a crucial key to develop the high affinity inhibitors for AQP4.
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Osuda Y, Shinzawa-Itoh K, Tani K, Maeda S, Yoshikawa S, Tsukihara T, Gerle C.2016
Author(s)
Osuda Y, Shinzawa-Itoh K, Tani K, Maeda S, Yoshikawa S, Tsukihara T, Gerle C.
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Journal Title
Microscopy
Volume: 65
Issue: 3
Pages: 263-267
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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