Elucidation of sodium translocation mechanism of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K14837
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Masuya Takahiro 京都大学, 農学研究科, 助教 (80803775)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 呼吸鎖酵素 / ユビキノン / コレラ菌 / ケミカルバイオロジー / Cryo-EM

Outline of Final Research Achievements

The sodium pumping NADH-quinone oxidoreductase (NQR) couples electron transfer from NADH to ubiquinone with sodium pumping. To investigate the coupling mechanism of redox reactions and sodium translocation, various quinones with different side chain structures were synthesized, and their activities were evaluated. The results revealed that while reduction was observed with quinones having no side chain or short side chain, sodium ion transport did not occur. This finding suggests that the side chain structure of quinones plays a crucial role in transport mechanisms.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

NQRはコレラ菌（Vibrio cholerae）などの多くの病原性細菌の生育に必須であり、機能の類似した哺乳類ミトコンドリアのプロトン輸送型NADH-キノン酸化還元酵素（呼吸鎖複合体-I）とは構造的にも進化的にも異なるため、病原性細菌に対する有望な創薬標的として注目されている。そのため、NQRの作用機構を明らかにすることは、NQRの基礎研究の進展に貢献するだけでなく、新規抗菌剤分子の設計戦略に資するところも大きい。