Elucidation of inhibition mechanism of kinesin motor to develop anti-cancer drugs
| 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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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP)2017
Author(s)
Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno S, Tanaka K, Hashimoto H.
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Journal Title
Journal of Biological Chemistry
Volume: 292
Issue: 43
Pages: 17658-17667
DOI
Related Report
Peer Reviewed / Open Access
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