| 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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| 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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