Elucidation of the molecular valve in the transporter to determine the direction of the transporter cycle

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Toho University
• Principal Investigator: MIYAUCHI Seiji 東邦大学, 薬学部, 教授 (30202352)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: トランスポーター / 分子弁 / 水素結合ネットワーク / 輸送サイクル / 基質認識機構 / モジュレーター

Outline of Final Research Achievements

To elucidate how the molecular valve can determine the direction of the transporter cycle in the transporter accompanying ion movement, we precisely determined the transports of human oligopeptide transporter (hPEPT1) and human Na+/monocarboxylate co-transporter (hSMCT1).
(1) We demonstrated using a chemical modification reagent for hydroxyl group, phenylmethylsulfonylfluoride (PMSF) that the hydroxyl group of Ser302 weakly forms the hydrogen-bonding with the imidazole of His57, which might keep the uptake activity optimum in the range of physiological intestinal pH.
(2) We elucidated with quantitative activity-structure relationship (QASR) that the molecular valve hSMCT1 might also determine the transport-direction of coupling Na+ ion and substrate.

Free Research Field

物理系薬学