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Study on the function of ND1 subunit, a key subunit of respiratory complex I

Research Project

Project/Area Number 23380064
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  京都大学, (連合)農学研究科(研究院), 教授 (20190829)

Co-Investigator(Renkei-kenkyūsha) MURAI Masatoshi  京都大学, 大学院・農学研究科, 助教 (80543925)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords細胞機能調節物質 / ミトコンドリア呼吸鎖酵素 / 複合体-I / アセトゲニン / 光親和性標識 / トシルケミストリー / ミトコンドリア / 阻害剤 / 呼吸鎖複合体-I / ND1サブユニット / 呼吸鎖阻害剤
Research Abstract

To elucidate the functional and structural aspects of the ND1 subunit, which is a key subunit of the membrane domain of bovine heart mitochondrial complex I (NADH-quinone oxidoreductase), I synthesized unique inhibitor probes acting to the ND1 and identified their binding sites via photoaffinity labeling experiment. In addition, I succeeded in site-specific chemical labeling (alkynylation) via ligand-directed tosyl (LDT) chemistry using acetogenin as a high affinity ligand against complex I.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (22 results)

All 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (10 results) Remarks (4 results)

  • [Journal Article] Site-specific chemical labeling of mitochondrial respiratory complex I through ligand-directed tosylate chemistry2014

    • Author(s)
      Masuya, T., Murai, M., Ifuku, K., Morisaka, H., and Miyoshi, H
    • Journal Title

      Biochemistry

      Volume: 53 Pages: 2307-2317

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Site-specific chemical labeling of mitochonodrial respiratory complex I through ligand-directed tosylate chemistry2014

    • Author(s)
      Takahiro Masutani, Masatoshi Murai, Kentaro Ifuku, Hironobu Morisaka, Hideto Miyoshi
    • Journal Title

      Biochemistry

      Volume: 53 Issue: 14 Pages: 2307-2317

    • DOI

      10.1021/bi500205x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of a methyl group on the γ-lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I2013

    • Author(s)
      Kojima, N., Abe, M., Suga, Y., Ohtsuki, K., Tanaka, T., Iwasaki, H., Yamashita, M., and Miyoshi, H
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 23 Pages: 1217-1219

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of a methyl group on theγ-lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I2013

    • Author(s)
      Naoto Kojima, Masato Abe, Yuki Suga, Kazufumi Ohtsuki, Tetsuaki Tanaka, Hiroki Iwasaki, Masayuki Yamashita, Hideto Miyoshi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 23 Issue: 5 Pages: 1217-1219

    • DOI

      10.1016/j.bmcl.2013.01.018

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fenpyroximate binds to the interface between PSST and 49 kDa subunits in mitochondrial NADH-ubiquinone oxidoreductase2012

    • Author(s)
      Shiraishi, Y., Murai, M., Sakiyama, N., Ifuku, K., and Miyoshi, H
    • Journal Title

      Biochemistry

      Volume: 51 Pages: 1953-1963

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and characterization of photoaffinity probe of acetogenin, a strong inhibitor of mitochondrial complex I2011

    • Author(s)
      Yamamoto, S., Abe, M., Nakanishi, S., Murai, M., and Miyoshi, H
    • Journal Title

      Tetrahedron Lett

      Volume: 52 Pages: 3090-3093

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Exploring interactions between the 49 kDa and ND1 subunits in mitochondrial NADH-ubiquinone oxidoreductase (complex I) by photoaffinity labeling2011

    • Author(s)
      Murai, M., Mashimo, Y., Hirst, J., and Miyoshi H
    • Journal Title

      Biochemistry

      Volume: 50 Pages: 6901-6908

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bis-THF motif of acetogenin binds to the third matrix-side loop of ND1 subunit in mitochondrial NADH-ubiquinone oxidoreductase2011

    • Author(s)
      Nakanishi, S., Abe, M., Yamamoto, S., Murai, M., and Miyoshi, H
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1807 Pages: 1170-1176

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] ミトコンドリアNADH-ユビキノン酸化還元酵素(複合体-I)の部位特異的化学修飾2014

    • Author(s)
      桝谷貴洋, 村井正俊, 三芳秀人
    • Organizer
      日本農芸化学会・平成26年度大会
    • Place of Presentation
      明治大学生田キャンパス
    • Year and Date
      2014-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア複合体-I の位置特異的化学修飾2014

    • Author(s)
      桝谷貴洋, 村井正俊, 三芳秀人
    • Organizer
      日本農薬学会・平成26年度大会
    • Place of Presentation
      京都大学農学部
    • Year and Date
      2014-03-14
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリアNADH-キノン酸化還元酵素の部位特異的化学修飾2014

    • Author(s)
      桝谷貴洋、村井正俊、三芳秀人
    • Organizer
      2014年度日本農芸化学会
    • Place of Presentation
      明治大学生田キャンパス
    • Related Report
      2013 Annual Research Report
  • [Presentation] 合成ユビキノンプローブを用いたミトコンドリアタンパク質Coq10 の解析2013

    • Author(s)
      村井正俊, 松延広平, 川向誠, 三芳秀人
    • Organizer
      日本生体エネルギー研究会・平成25年度討論会
    • Place of Presentation
      静岡県コンベンションアーツセンター・グランシップ
    • Year and Date
      2013-12-19
    • Related Report
      2013 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2013

    • Author(s)
      村井正俊, 白石悠助, 崎山直人, 三芳秀人
    • Organizer
      日本農芸化学会・平成25年度大会
    • Place of Presentation
      東北大学川内北キャンパス
    • Year and Date
      2013-03-26
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア複合体-I に作用するキナゾリン型阻害剤の結合部位の同定2013

    • Author(s)
      浅野周, 村井正俊, 三芳秀人
    • Organizer
      日本農芸化学会・平成25年度大会
    • Place of Presentation
      東北大学川内北キャンパス
    • Year and Date
      2013-03-26
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア複合体-I 阻害剤としてのアミロライド類縁体の合成と作用機構2013

    • Author(s)
      土生沙綾子, 村上園美, 村井正俊, 三芳秀人
    • Organizer
      日本農芸化学会・平成25年度大会
    • Place of Presentation
      東北大学川内北キャンパス
    • Year and Date
      2013-03-26
    • Related Report
      2013 Final Research Report
  • [Presentation] ユビキノンプローブの合成とユビキノン結合性タンパク質Coq10の解析2013

    • Author(s)
      三芳秀人
    • Organizer
      2013年度日本農芸化学会
    • Place of Presentation
      東北大学川内北キャンパス
    • Related Report
      2012 Annual Research Report
  • [Presentation] ミトコンドリア複合体-I におけるアセトゲニン結合部位の同定2012

    • Author(s)
      中西佐予, 安部真人, 村井正俊, 三芳秀人
    • Organizer
      日本農芸化学会・平成24年度大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-24
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア複合体-Iの阻害剤結合部位の同定:フェンピロキシメートの結合部位2012

    • Author(s)
      白石悠助, 他3名、4番目
    • Organizer
      日本農薬学会第37回大会
    • Place of Presentation
      岡山大学
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 生物機能制御化学研究室ホームページ

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Remarks] 生物機能制御化学研究室ホームページ

    • URL

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

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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