2023 Fiscal Year Final Research Report
Structural study of regulation mechianism of the nuclear receptor proteins related to drug metabolism
Project/Area Number |
21K06493
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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Research Institution | Kumamoto University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
森岡 弘志 熊本大学, 大学院生命科学研究部(薬), 教授 (20230097)
関口 光広 石川県立大学, 生物資源環境学部, 准教授 (40822490)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | 核内受容体 / PXR / CAR / 分子間相互作用 / 薬物間相互作用 |
Outline of Final Research Achievements |
Pregnane X Receptor (PXR) and Constitutive Androstane Receptor (CAR) function as sensor proteins for xenobiotics such as drugs, and association of agonists induce the expression of proteins involved in drug metabolism. Therefore, PXR and CAR are involved in drug-drug interactions and are related to resistance of cancers for drug. To elucidate structural mechanisms for regulation of functions of PXR and CAR, biophysical studies for analyze interaction between PXR and CAR with both the coactivator and the corepressor proteins. Moreover, we attempted to establish a convenient method for evaluation of interactions between PXR and CAR with both the coactivator and the corepressor proteins.
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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 |
本研究で構築したGST(+)/GST(-)ヘテロ二量体を用いることで2種類の任意のタンパク質同士で人為的に二量体を形成させることが可能である。加えて、GST(+)/GST(-)ヘテロ二量体はグルタチオンを固定化した固体表面に結合させることが可能である。そのため、結合が弱いタンパク質同士のCryo-EMやX線回折等による立体構造解析への応用や、2種類の酵素からなる人工的なヘテロ二量体を固体表面上に結合させた固定化酵素への応用、二種類の別々の抗原を認識する抗体由来の一本鎖抗体を用いた二重特異性抗体など、今後、様々な応用が期待される。
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