| Project/Area Number |
25860050
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
YAMAMOTO Soh 札幌医科大学, 医学部, 助教 (10588479)
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| Research Collaborator |
ITOH Hideaki
KUBOTA Hiroshi
YAMAGUCHI Yoshiki
YOKOTA Shin-ichi
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子シャペロン / HSP70 / HSP90 / HOP / タンパク質折りたたみ |
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| Outline of Final Research Achievements |
Co-chaperone HOP (HSP70/HSP90 Organizing Protein) assists protein transfer in the HSP70 and HSP90 dependent protein-folding pathway. HOP highly expresses and forms the complexes with HSP70 and HSP90 in cancer cells. In the present study, we investigated (1) identification the inhibitor of HOP for cancer therapy using chemical library and (2) biochemical analysis of ATPase activity of HOP.
(1) We identified binding chemicals to HOP from thirty thousand drugs at first-screening step. We found the twenty-eight drugs that specifically bound to full-length HOP and TPR2A region at secondly-screening step. (2) We determined the ATP hydrolysis rate and dissociation constant, are 3.8 x 10-3mol ATP/mol HOP/min and 350 μM, respectively. 1-359 (TPR1-TPR2A) was required for ATP hydrolysis and interaction with ATP. We demonstrated the HOP changes its conformation by ATP hydrolysis using NMR analysis and protease sensitivity assay.
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