| Project/Area Number |
26670014
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
Kato Hiroaki 京都大学, 薬学研究科(研究院), 教授 (90204487)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 構造生物学 / 受容体・膜輸送 / 薬理学 / X線結晶学 |
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| Outline of Final Research Achievements |
We discovered that a repleacement of a Gln residue with Ala in a eukaryotic P-glycoprotein, euP-gp induced an increase of the basal ATP hydrolysis enzyme activity independent with a transport substrate, suggesting the Gln residue plays an important role in the coupling between ATP hydrolysis and active transport. To reveal this proposition, we determined the crystal structure of euP-gp and observed that the Gln residue connects an Ala residue in an alpha-helix of the other subunit by van der Waals force. This interaction may restrict the structural exchange between inward-open and outward-open states of the transporter, allowing to accumulate a torque that drives the reverse structural exchange of the transporter.
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