2020 Fiscal Year Final Research Report
Structural analysis of MexY for the basis of drug discovery against multidrug-resistant Pseudomonas aeruginosa
Project/Area Number |
19K23825
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0802:Biomedical structure and function and related fields
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Research Institution | Osaka University |
Principal Investigator |
Tsutsumi Kenta 大阪大学, 蛋白質研究所, 特任研究員 (60844785)
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | 構造解析 / クライオ電子顕微鏡 / 単粒子解析 / 薬剤耐性 / 膜蛋白質 |
Outline of Final Research Achievements |
In order to analyze the structure of MexY, which is an effective drug target for multidrug-resistant Pseudomonas aeruginosa and whose three-dimensional structure has not been reported, I screened solubilization and purification methods. For the aminoglycoside-resistant strain PA7, I succeeded in purifying the functional trimer using detergents or a polymer that forms nanodiscs directly from the membrane. The amino acid sequence suggested that the C-terminus of MexY may contribute to the stabilization of the functional trimer. Unfortunately, I was not able to achieve structural analysis using cryo-electron microscopy, but this research may be a step toward the determination of the structure of MexY.
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Free Research Field |
構造生物学
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Academic Significance and Societal Importance of the Research Achievements |
臨床で多用されているアミノグルコシド系統の抗生物質を緑膿菌のポンプの中で唯一排出することが可能なRND型多剤排出ポンプの中枢を担う MexYの機能を阻害する方法が開発できれば、これまで多剤耐性緑膿菌に効果のなかったアミノグリコシド系の抗生物質が使用できる可能性が出てくる。本研究は未だに有効な手立てのない多剤耐性緑膿菌感染症に対する有効な手段となり、本研究は阻害剤の開発に向けた一歩となったと考えられる。
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