Investigation for the mechanism of the gastric proton pump that generates the steepest cation gradient
| Project/Area Number |
26711005
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
Abe Kazuhiro 名古屋大学, 細胞生理学研究センター, 准教授 (60596188)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | P型ATPase / 膜タンパク質 / 電子顕微鏡 / 膜輸送体 / 胃プロトンポンプ / P-type ATPase / 能動輸送体 / H,K-ATPase / 電子線結晶学 / 生化学 / 極低温電子顕微鏡 |
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| Outline of Final Research Achievements |
Gastric proton pump is a membrane protein responsible for the gastric acid secretion, therefore it is a molecular target for the anti-ulcer drug. In this research, we attempt to determine its structure by both electron and X-ray crystallography, and establish a large-scale expression system using mammalian cells for the functional analysis and X-ray crystallography.
We proposed the binding model of acid suppressants to the gastric proton pump, by using electron crystallographic structure analyzed at 6.5 A resolution, which is conformed by the mutagenesis and derivatives of acid suppressants.
Furthermore, we successfully established the mammalian cell expression system, which allow us to generate 3D crystals for X-ray. Determined structure reveals the mechanism of proton extrusion to the highly acidic solution of the stomach.
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Report
(4 results)
Research Products
(14 results)
