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Mechanism of inhibition of ATP synthase by phytopolyphenols

Research Project

Project/Area Number 24790048
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionIwate Medical University

Principal Investigator

SEKIYA Mizuki  岩手医科大学, 薬学部, 助教 (70509033)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsATP合成酵素 / ポリフェノール / F-ATPase / ATP 合成酵素 / FoF1 / 阻害剤
Research Abstract

ATP synthase generate ATP using energy from a proton motive force across the membrane. Their mechanism includes subunits rotation, which are essential for energy coupling between proton transport and catalysis. We have studied the inhibitory effects and inhibition mechanism of phytopolyphenols. I found curcumin and its analogues inhibited ATP synthase F1 sector. We also found piceatannol and beta-gamma interface mutation affect the rate-limiting transition step, even though they perturb physically separated rotor-stator interactions. These data indicate that both rotor-stator interaction sites contribute to formation of the rate limiting transition state.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 2 results) Presentation (12 results)

  • [Journal Article] Rotating proton pumping ATPases : subunit /subunit interactions and thermodynamics2013

    • Author(s)
      M. Nakanishi-Matsui, M. Sekiya, and M. Futai
    • Journal Title

      IUBMB Life

      Volume: 65 Pages: 247-254

    • Related Report
      2013 Final Research Report
  • [Journal Article] Rotating proton pumping ATPases: Subunit/subunit interactions and thermodynamics.2013

    • Author(s)
      M. Nakanishi-Matsui(責任著者), M. Sekiya, and M. Futai
    • Journal Title

      IUBMB-Life

      Volume: 65 Issue: 3 Pages: 247-254

    • DOI

      10.1002/iub.1134

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Binding of the phytopolyphenol piceatannol disruptsβ/γsubunit interactions and the rate limiting step of steady state rotational catalysis in the Escherichia coli F_1-ATPase2012

    • Author(s)
      M. Sekiya, R. K. Nakamoto, M. Nakanishi-Matsui and M. Futai
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 22771-22780

    • Related Report
      2013 Final Research Report
  • [Journal Article] Rotational catalysis in proton pumping ATPases : from E. coli F-ATPase to mammalian V-ATPase2012

    • Author(s)
      M. Futai, M. Nakanishi-Matsui, H. Okamoto, M. Sekiya and R. K. Nakamoto
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1817 Pages: 1711-1721

    • Related Report
      2013 Final Research Report
  • [Journal Article] Binding of phytopolyphenol piceatannol disrupts β/γ subunit interactions and rate-limiting step of steady state rotational catalysis in Escherichia coli F1-ATPase.2012

    • Author(s)
      M. Sekiya, R. K. Nakamoto, M. Nakanishi -Matsui and M. Futai
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Issue: 27 Pages: 22771-22780

    • DOI

      10.1074/jbc.m112.374868

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ポリエンα-ピロンによるATP合成酵素阻害メカニズム2014

    • Author(s)
      關谷瑞樹、鈴木彩香、二井將光、中西(松井)真弓
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-30
    • Related Report
      2013 Final Research Report
  • [Presentation] クルクミンによるATP合成酵素阻害メカニズムの解析2013

    • Author(s)
      關谷瑞樹、久坂亮介、西山枝里、千葉瑛子、佐藤桃恵、岩本(木原)昌子、二井將光、中西(松井)真弓
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-12
    • Related Report
      2013 Final Research Report
  • [Presentation] ポリフェノール類によるATP合成酵素阻害メカニズムの解析2013

    • Author(s)
      關谷瑞樹、Robert K. Nakamoto、吉田秀成、西山枝里、(松井)真弓、二井將光
    • Organizer
      FAOBMB Mini-Symposium
    • Place of Presentation
      岩手矢巾
    • Year and Date
      2013-04-06
    • Related Report
      2013 Final Research Report
  • [Presentation] クルクミン類縁体によるATP合成酵素の阻害作用2013

    • Author(s)
      千葉瑛子、佐藤桃恵、關谷瑞樹、久坂亮介、山越博幸、高山亜紀、柴田浩行、中西(松井)真弓、岩渕好治、二井將光
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] クルクミンによるATP合成酵素の阻害機構の解析2013

    • Author(s)
      久坂亮介、關谷瑞樹、千葉瑛子、佐藤桃恵、岩本(木原)昌子、中西(松井)真弓、二井將光
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 千葉瑛子, 佐藤桃恵, 関谷瑞樹, 久坂亮介, 山越博幸, 高山亜紀, 柴田浩行, 中西(松井)真弓, 岩渕好治, 二井將光2013

    • Author(s)
      クルクミン類縁体によるATP合成酵素の阻害作用
    • Organizer
      日本薬学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 久坂亮介, 関谷瑞樹, 千葉瑛子, 佐藤桃恵, 岩本(木原)昌子, 中西(松井)真弓, 二井將光2013

    • Author(s)
      クルクミンによるATP合成酵素の阻害機構の解析
    • Organizer
      日本薬学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 一分子観察によるポリフェノール類のATP合成酵素阻害機構2012

    • Author(s)
      關谷瑞樹、Robert K. Nakamoto、中西(松井)真弓、二井將光
    • Organizer
      生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 関谷瑞樹, Robert K. Nakamoto, 中西(松井)真弓, 二井將光2012

    • Author(s)
      一分子観察によるポリフェノール類の ATP合成酵素阻害機構
    • Organizer
      生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] ポリフェノール類によるATP合成酵素阻害メカニズムの解析

    • Author(s)
      〇關谷瑞樹、Robert K. Nakamoto、 吉田秀成、西山枝里、(松井)真弓、 二井將光
    • Organizer
      FAOBMB Mini-Symposium
    • Place of Presentation
      岩手矢巾
    • Related Report
      2013 Annual Research Report
  • [Presentation] クルクミンによるATP合成酵素阻害メカニズムの解析

    • Author(s)
      〇關谷瑞樹、久坂亮介、西山枝里、 千葉瑛子、佐藤桃恵、岩本(木原)昌子、二井將光、中西(松井)真弓
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] ポリエン α-ピロンによるATP 合成酵素阻害メカニズム

    • Author(s)
      〇關谷瑞樹、鈴木彩香、二井將光、 中西(松井)真弓
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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