| Project/Area Number |
17K07316
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Yokoyama Hideshi 東京理科大学, 薬学部生命創薬科学科, 准教授 (70433208)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | X線結晶構造解析 / 等温滴定型カロリメトリー / キネシンモーター / 阻害剤 / キネシン / モータータンパク質 / 結晶化 / 構造解析 |
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| Outline of Final Research Achievements |
In this study, I tried to determine the structures of the mitotic kinesin Eg5 and CENP-E and the complexes with their inhibitors were determined to elucidate the binding and inhibition mechanisms of the inhibitors and to develop novel anti-cancer drugs. For Eg5 motor domain, I performed X-ray crystal structure determination and isothermal titration calorimetry analyses, and elucidated the inhibition mechanisms. For CENP-E motor domain, I determined the crystal structure in higher resolution than the previous report, and elucidate the structural feature.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞分裂期特異的なキネシンモータータンパク質CENP-EやEg5とそれらの阻害剤との複合体構造解析による、阻害剤の結合阻害の機構を解明することで、新規な抗がん剤を設計する構造基盤が得られた。既存のタキサン、ビンカアルカロイドなどの微小管阻害剤と異なり、キネシンモーターの阻害剤は非分裂期の微小管には作用しないため、副作用の少ない抗がん剤のリード化合物として期待できる。
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