Structural analysis of bafilomycin bound to V-ATPase for elucidating its inhibition mechanism based on synthetic chemistry

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K01821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Osaka University
• Principal Investigator: Tsuchikawa Hiroshi 大阪大学, 理学研究科, 助教 (30460992)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: バフィロマイシン / ATPアーゼ / フッ素標識 / 化学合成 / 構造解析 / 固体NMR

Outline of Final Research Achievements

The structural analysis of bafilomycin (Baf), a specific inhibitor towards vacuolar-type ATPase (V-ATPase), was performed based on synthetic chemistry. First, the preparation of bioactive 19F-labelled Baf required for solid-state NMR measurement was achieved by synthesizing several Baf derivatives and evaluating their V-ATPase inhibitory effect. Next, behavior analysis of active and inactive F-Baf derivatives in model membrane resulted in finding the remarkable difference of their mobility, which may probably relate to the difference of their activity. Moreover, a large-scale preparation of V-ATPase as proteoliposomes was successfully accomplished and the structural analysis of F-Baf bound to V-ATPase was examined by solid-state NMR.

Free Research Field

ケミカルバイオロジー、合成有機化学