| Project/Area Number |
18K14637
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43020:Structural biochemistry-related
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| Research Institution | Tsuyama National College of Technology (2019-2021)
Osaka University (2018) |
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Principal Investigator |
Takagi Kenji 津山工業高等専門学校, 総合理工学科, 准教授 (90647322)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | プロテアソーム / X線結晶構造解析 / ゲル内結晶化 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop a highly active new drug based on the complex structure of proteasome and compound, which is difficult to analyze. Initially, we were conducting research on the assumption that hydrophobic compounds would be immersed and bonded after the formation of proteasome crystals, with reference to the in-gel crystallization method. Due to the difficulty, we changed to targeting proteasome activity regulators with low molecular weight and unstructured. As a result, we completed the construction of an expression system for the novel plant proteasome chaperone PBAC5 and established a stable PBAC5 purification method. We also succeeded in purifying a complex with PBAC1, which is a homologue of yeast Pba1.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、当初ゲル内結晶化法を用いて、プロテアソームと新規薬剤の構造決定を目指していたが、プロテアソーム結晶の場合、ゲル内でも有機溶媒の影響が大きく、分解能が十分に上がらなかった。今後この方法に適したターゲットや結晶を選択し、結晶化法や浸漬法に改良を加えることで構造解析が可能になると考えられる。また、プロテアソーム分子集合については不明な部分が多く、PBAC5-PBAC1複合体の安定発現系の構築により、機能解明が早まると考えられる。
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