| 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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| 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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