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Exploring the function of membrane domain of mitochondrial complex-I on the basis of synthesis of inhibitor probes

Research Project

Project/Area Number 20380068
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionKyoto University

Principal Investigator

MIYOSHI Hideto  Kyoto University, 大学院・農学研究科, 教授 (20190829)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2008: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords細胞機能調節物質 / ミトコンドリア / 複合体-I / 光親和性標識 / 阻害剤 / アセトゲニン / ND1サブユニット / 呼吸鎖酵素 / ペプチド化学 / 生体エネルギー
Research Abstract

To identify the binding site of quinazoline and Dlac-acetogenin in bovine heart mitochondrial complex-I (NADH-quinone oxidoreductase), we synthesized photoreactive probes [^<125>I]AzQ and [^<125>I]DAA, respectively. We revealed that [^<125>I]AzQ binds at the interface of the 49 kDa and ND1 subunits. On the other hand, careful examination of the fragmentation patterns of the ND1 subunit cross-linked by [^<125>I]DAA strongly suggested that the cross-linked residues are located at two different sites in the third matrix-side loop connecting the 5th and 6th transmembrane helices.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (24 results)

All 2011 2010 2009 2008 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (10 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Exploring the binding site of Δlac-acetogenin in bovine heart mitochondrial2010

    • Author(s)
      Kakutani, N., Murai, M., Sakiyama, N., Miyoshi, H.
    • Journal Title

      NADH-ubiquinone oxidoreductase, Biochemistry 49

      Pages: 4794-4803

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the ubiquinone binding site in alternative NADH-quinone oxidoreductase of Saccharomyces cerevisiae by photoaffinity labeling2010

    • Author(s)
      Murai, M., Yamashita, T., Senoh, M., Mashimo, Y., Kataoka, M., Kosaka, H., Matsuno-Yagi, A., Yagi, T., Miyoshi, H.
    • Journal Title

      Biochemistry 49

      Pages: 2973-2980

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Exploring the Binding Site of Δlac-Acetogenin in Bovine Heart Mitochondrial NADH-Ubiquinone Oxidoreductase.2010

    • Author(s)
      角谷伸行、村井正俊、崎山直人、三芳秀人
    • Journal Title

      Biochemistry

      Volume: 49 Pages: 4794-4803

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the ubiquinone binding site in the alternative NADH-quinone oxidoreductase of Saccharomyces cerevisiae by photoaffinity labeling2010

    • Author(s)
      村井正俊, ら (以下8名)
    • Journal Title

      Biochemistry 49

      Pages: 2973-2980

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploring the binding site of acetogenin in the NDI subunit of bovine mitochondrial complex2009

    • Author(s)
      Sekiguchi, K., Murai, M.,Mivoshi, H.
    • Journal Title

      I, Biochim. Biophys. Acta(Bioenergetice) 1787

      Pages: 1106-1111

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the inhibitor binding site in mitochondrial NADH-ubiquinone oxidoreductase by photoaffinity labeling using a quinazoline-type inhibitor2009

    • Author(s)
      Murai, M., Sekiguchi, K., Nishioka, T., Miyoshi,H.
    • Journal Title

      Biochemistry 48

      Pages: 688-698

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the inhibitor binding site in maitochondrial NADH-ubiauinone oxidoreductase by2009

    • Author(s)
      Masatoshi Murai, Koji Sekiguchi, Takaaki Nishioka, Hideto Miyoshi
    • Journal Title

      Biochemistry 48

      Pages: 688-698

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and characterization of new piperazine-type inhibitors for mitochondrial NADH-ubiquinone oxidoreductase(complex I)2008

    • Author(s)
      Ichimaru, N., Murai, M., Kakutani, N, Kako, J., Ishihara, A., Nakagawa, Y., Nishioka, T., Yagi, T., Miyoshi
    • Journal Title

      Biochemitsry 47

      Pages: 10816-10826

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic fhnction of the spacer region of acetogen ins in the inhibition of bovine mitochondrial NADH-ubiquinone oxidoreductase (complex I)2008

    • Author(s)
      Abe, M., Kubo, A., Yamamoto, S., Hatoh, Y., Murai, M., Hattori, Y., Makabe, H., Nishioka, T., Miyoshi, H.
    • Journal Title

      Biochemistry 47

      Pages: 6260-6266

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] ミトコンドリア複合体-Iに作用する光反応性フェンピロキシメートの結合部位の同定2011

    • Author(s)
      村井正俊、崎山直人、白石、祐輔、安部真人、三芳秀人
    • Organizer
      日本農芸化学会・平成23年度大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2011-03-27
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-Iにおけるアセトゲニンの結合部位の同定2011

    • Author(s)
      中西佐予、安部真人、山本修平、村井正俊、三芳秀人
    • Organizer
      日本農芸化学会・平成23年度大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2011-03-27
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-Iに作用する光反応性フェンピロキシメートの結合部位の同定(1)2011

    • Author(s)
      村井正俊、崎山直人、白石、祐輔、安部真人、三芳秀人
    • Organizer
      日本農薬学会・平成23年度大会
    • Place of Presentation
      玉川大学
    • Year and Date
      2011-03-17
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-Iに作用する光反応性フェンピロキシメートの結合部位の同定(2)2011

    • Author(s)
      崎山直人、村井正俊、白石、祐輔、安部真人、三芳秀人
    • Organizer
      日本農薬学会・平成23年度大会
    • Place of Presentation
      玉川大学
    • Year and Date
      2011-03-17
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-I阻害剤Δlac-アセトゲニンの結合部位の解明2010

    • Author(s)
      村井正俊、角谷信至、崎山直人、三芳秀人
    • Organizer
      生体エネルギー研究会・平成22年討論会
    • Place of Presentation
      大阪大学銀杏会館
    • Year and Date
      2010-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-I阻害剤Δlac-アセトゲニンの結合部位の同定2010

    • Author(s)
      村井正俊、角谷信至、崎山直人、三芳秀人
    • Organizer
      日本農薬学会・平成22年度大会
    • Place of Presentation
      北海道大学学術交流会館
    • Year and Date
      2010-05-29
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-l阻害剤△lac-アセトゲニンの結合部位の同定2010

    • Author(s)
      村井正俊, ら
    • Organizer
      日本農芸化学会2010年度大会
    • Place of Presentation
      東京大学駒場キャンパス
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 光親和性標識法によるキナゾリン型阻害剤のミトコンドリア複合体-Iにおける結合部位の解明2009

    • Author(s)
      村井正俊、関口孝治、三芳秀人
    • Organizer
      生体エネルギー研究会・平成20年討論会
    • Place of Presentation
      東京医科歯科大学5号館講堂
    • Year and Date
      2009-11-06
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリア複合体-Iに作用するアセトゲニンの結合部位の解析2009

    • Author(s)
      村井正俊、関口孝治、三芳秀人
    • Organizer
      日本農薬学会・平成21年度大会
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2009-03-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 光親和性標識法によるミトコンドリア複合体-I阻害剤キナゾリンの結合部位の解析2009

    • Author(s)
      関口孝治、村井正俊、三芳秀人
    • Organizer
      日本農薬学会・平成21年度大会
    • Place of Presentation
      東京大学弥生講堂
    • Year and Date
      2009-03-18
    • Related Report
      2010 Final Research Report
  • [Book] 月刊誌『化学』最近のトピックス「呼吸鎖酵素最後の秘境:複合体-Iの構造と機能」2011

    • Author(s)
      村井正俊、三芳秀人
    • Total Pages
      2
    • Publisher
      化学同人
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.biofunc-chem.kais.kyoto-u.acjp/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.biofunc-chem.kais.kyoto-u.ac.jp/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.biofunc-chem.kais.kyoto-u.ac.jp/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.biofunc-chem.kais.kyoto-u.ac.jp/

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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