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Reaction Mechanism of Heme Oxygenase

Research Project

Project/Area Number 21350087
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionTohoku University

Principal Investigator

IKEDA-SAITO Masao  東北大学, 多元物質科学研究所, 教授 (70302239)

Co-Investigator(Renkei-kenkyūsha) MATSUI Toshitaka  東北大学, 多元物質科学研究所, 講師 (90323120)
UNO Masaki  茨城大学, フロンティア応用原子科学研究センター, 准教授 (10359549)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2009: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywordsヘム / 酸素活性化 / 結晶構造解析 / ベルドヘム / 反応機構 / 構造活性相関 / ヘム代謝 / メスバウアー
Research Abstract

Enzymatic heme degaradation by heme oxygenase, especially its rate-limiting ring opening step, have been studied in detail. Spectroscopic analysis reveals the formation of a ferryl species as a ring opening intermediate. Crystallographic study on an intermediate-enzyme complex combined with theoritical calculations finally elucidate the rate-limiting reaction. We also examined a novel heme cleavage reaction to clarify its mechanism and the new heme catabolites were succesufully detected from cultured mammalian cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (55 results)

All 2011 2010 2009

All Journal Article (17 results) (of which Peer Reviewed: 16 results) Presentation (37 results) Book (1 results)

  • [Journal Article] Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cell as a ligand of Bach22011

    • Author(s)
      M. Watanabe-Matsui, A. Muto, T. Matsui, A. Itoh-Nakadai, O. Nakajima, K. Murayama, M. Yamamoto, M. Ikeda-Saito, K. Igarashi
    • Journal Title

      Blood

      Volume: 117 Pages: 5438-5448

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 金属タンパク質のX線結晶構造解析:ヘム分解酵素の反応中間体2011

    • Author(s)
      海野昌喜, 松井敏高, 齋藤正男
    • Journal Title

      日本結晶学会誌

      Volume: 53 Pages: 213-218

    • NAID

      10029371570

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] ヘム分解における酸素活性化:活性酸素の有効利用2011

    • Author(s)
      松井敏高
    • Journal Title

      生物物理

      Volume: 51 Pages: 132-133

    • NAID

      10029139987

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Binding and selectivity of the marine toxins neodysiherbaine A, and its synthetic analogues, to GluK1 and GIuK2 kainate receptors2011

    • Author(s)
      M.Unno, M.Shinohara, K.Takayama, H.Tanaka, K.Teruya, K.Doh-ura, R.Sakai, M.Sasaki, M.Ikeda-Saito
    • Journal Title

      Journal of Molecular Biology

      Volume: 413 Issue: 3 Pages: 667-683

    • DOI

      10.1016/j.jmb.2011.08.043

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heme regulates B cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach22011

    • Author(s)
      M.Watanabc-Matsui, et al.
    • Journal Title

      Blood

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heme oxygenase reveals its strategy for catalyzing three successive oxygenation reactions2010

    • Author(s)
      T. Matsui, M. Unno, M. Ikeda-Saito
    • Journal Title

      Acc. Chem. Res.

      Volume: 43 Pages: 240-247

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dioxygen activation for self-degradation of heme : Reaction mechanism and regulation of heme oxygenase.2010

    • Author(s)
      T. Matsui, M. Iwasaki, R. Sugiyama, M. Unno, M. Ikeda-Saito
    • Journal Title

      Inorg. Chem

      Volume: 49 Pages: 3602-3609

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Solution 1H NMR characterization of substrate-free C. diphtheriae heme oxygenase : Pertinence for determining magnetic axes in paramagnetic substrate complexes.2010

    • Author(s)
      Z. Du, M. Unno, T. Matsui, M. Ikeda-Saito, G. N. La Mar
    • Journal Title

      J. Inorg. Biochem

      Volume: 104 Pages: 1063-1070

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enzymatic ring-opening mechanism of verdoheme by the heme oxygenase : A combined X-ray crystallography and QM/MM study.2010

    • Author(s)
      W. Lai, H. Chen, T. Matsui, K. Omori, M. Unno, M. Ikeda-Saito, S. Shaik
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 132 Pages: 12960-12970

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dioxygen activation for self-degradation of heme : Reaction mechanism and regulation of heme oxygenase.2010

    • Author(s)
      T.Matsui, et al.
    • Journal Title

      Inorganic Chemistry

      Volume: 49 Pages: 3602-3609

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solution ^1H NMR characterization of substrate-free C.diphtheriae heme oxygenase : Pertinence for determining magnetic axes in paramagnetic substrate complexes2010

    • Author(s)
      Z.Du, et al.
    • Journal Title

      Journal of Inorganic Biochemistry

      Volume: 104 Pages: 1063-1070

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enzymatic ring-opening mechanism of verdoheme by the heme oxygenase : A combined X-ray crystallography and QM/MM study.2010

    • Author(s)
      W.Lai, et al.
    • Journal Title

      Journal of the American Chemical Society

      Volume: 132 Pages: 12960-12970

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heme oxygenase reveals its strategy for catalyzing three successive oxygenation reactions.2010

    • Author(s)
      T.Matsui, et al.
    • Journal Title

      Accounts of Chemical Research 43

      Pages: 240-247

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dioxygen activation for self-degradation of heme : Reaction mechanism and regulation of heme oxygenase.2010

    • Author(s)
      T.Matsui, et al.
    • Journal Title

      Inorganic Chemistry (未定, 印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heme-dependent autophosphorylation of a heme sensor kinase, ChrS, from Corynebacterium diphtheriae reconstituted in proteoliposomes.2009

    • Author(s)
      Y. Ito, S. Nakagawa, A. Komagata, M. Ikeda-Saito, Y. Shiro, H. Nakamura
    • Journal Title

      FEBS Lett.

      Volume: 583 Pages: 2244-2248

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heme-dependent autophosphorylation of a heme sensor kinase, ChrS, from Corynebacterium diphtheriae reconstituted in proteoliposomes.2009

    • Author(s)
      Y.Ito, et al.
    • Journal Title

      FEBS Letters 583

      Pages: 2244-2248

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      M.Unno, et al.
    • Journal Title

      Nanohybridization of Organic-Inorganic Materials(Springer)

      Pages: 193-217

    • Related Report
      2009 Annual Research Report
  • [Presentation] Heme oxygenase catalytic mechanism2011

    • Author(s)
      M.Ikeda-Saito
    • Organizer
      15th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Vancouver, Canada(招待講演)
    • Year and Date
      2011-08-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ring-opening mechanism of verdoheme by heme oxygenase2011

    • Author(s)
      T. Matsui, M. Ikeda-Saito
    • Organizer
      ICBIC 15
    • Place of Presentation
      Canada, Vancouver
    • Year and Date
      2011-08-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Heme oxygenase catalytic mechanism2011

    • Author(s)
      M. Ikeda-Saito, M. Unno, T. Matsui
    • Organizer
      15th International conference on biological inorganic chemistry
    • Place of Presentation
      Canada, Vancouver
    • Year and Date
      2011-08-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Ring-opening mechanism of verdoheme by heme oxygenase2011

    • Author(s)
      T.Matsui
    • Organizer
      15th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2011-08-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Heme oxygenase catalytic mechanism2011

    • Author(s)
      M. Ikeda-Saito, T. Matsui, M. Unno
    • Organizer
      International symposium on activation of dioxygen and homogeneous catalyst
    • Place of Presentation
      Japan, Nago
    • Year and Date
      2011-07-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Heme oxygenase catalytic mechanism2011

    • Author(s)
      M.Ikeda-Saito
    • Organizer
      International symposium on activation of dioxygen and homogeneous catalyst
    • Place of Presentation
      名護(招待講演)
    • Year and Date
      2011-07-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Heme oxygenase catalytic mechanism2010

    • Author(s)
      M. Ikeda-Saito, T. Matsui, M. Unno
    • Organizer
      Pacifichem 2010
    • Place of Presentation
      U. S. A., Honolulu
    • Year and Date
      2010-12-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Heme oxygenase catalytic mechanism2010

    • Author(s)
      M.Ikeda-Saito
    • Organizer
      Pacifichem 2010
    • Place of Presentation
      米国・ホノルル
    • Year and Date
      2010-12-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ring-opening mechanism of verdoheme catalyzed by heme oxygenase2010

    • Author(s)
      T. Matsui, M. Ikeda-Saito
    • Organizer
      The International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      USA, Honolulu
    • Year and Date
      2010-12-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Ring Opening Mechanism of Verdoheme Catalyzed by Heme Oxygenase2010

    • Author(s)
      T.Matsui
    • Organizer
      Pacifichem 2010
    • Place of Presentation
      米国・ホノルル
    • Year and Date
      2010-12-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヘム分解酵素によるベルドヘム開環メカニズム2010

    • Author(s)
      松井敏高, 海野昌喜, 齋藤正男
    • Organizer
      第43回酸化反応討論会
    • Place of Presentation
      東京
    • Year and Date
      2010-11-13
    • Related Report
      2011 Final Research Report
  • [Presentation] ヘムオキシゲナーゼによるベルドヘム開環メカニズム2010

    • Author(s)
      松井敏高
    • Organizer
      第43回酸化反応討論会
    • Place of Presentation
      東京大学
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ring Opening Mechanism of Verdoheme Catalyzed by Heme Oxygenase2010

    • Author(s)
      T.Matsui
    • Organizer
      第48回日本生物物理学会年会
    • Place of Presentation
      東北大学
    • Year and Date
      2010-09-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ring opening mechanism of verdoheme catalyzed by heme oxygenase2010

    • Author(s)
      T. Matsui, M. Unno, M. Ikeda-Saito
    • Organizer
      第48回日本生物物理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Catalytic mechanism of heme oxygenase, a central enzyme for heme catabolism2010

    • Author(s)
      M. Ikeda-Saito, T. Matsui, M. Unno
    • Organizer
      1st Asian chemical biology conference
    • Place of Presentation
      Korea, Seoul
    • Year and Date
      2010-06-25
    • Related Report
      2011 Final Research Report
  • [Presentation] Catalytic mechanism of heme oxygenase, a central enzyme for heme catabolism2010

    • Author(s)
      M.Ikeda-Saito
    • Organizer
      1st Asian chemical biology conference
    • Place of Presentation
      韓国・ソウル
    • Year and Date
      2010-06-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヘムオキシゲナーゼによるベルドヘム開環反応2010

    • Author(s)
      松井敏高, 海野昌喜, 齋藤正男
    • Organizer
      第37回生体分子科学討論会
    • Place of Presentation
      山口
    • Year and Date
      2010-06-19
    • Related Report
      2011 Final Research Report
  • [Presentation] ヘムオキシゲナーゼによるベルドヘム開環反応2010

    • Author(s)
      松井敏高
    • Organizer
      第37回生体分子科学討論会
    • Place of Presentation
      山口大学
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 構造を基にしたグルタミン酸受容体, GluR5GluR6選択的化合物の設計2009

    • Author(s)
      海野昌喜, 篠原正将, 高山昴一郎, 渡邉朋子, 田中秀治, 酒井隆一, 佐々木誠, 齋藤正男
    • Organizer
      2009年日本結晶学会年会
    • Place of Presentation
      兵庫県西宮市
    • Year and Date
      2009-12-05
    • Related Report
      2011 Final Research Report
  • [Presentation] 構造を基にしたグルタミン酸受容体GluR5, GluR6選択的化合物の設計2009

    • Author(s)
      海野昌喜
    • Organizer
      2009年日本結晶学会年会
    • Place of Presentation
      西宮
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] ベルドヘムーヘムオキシゲナーゼ複合体の構造解析2009

    • Author(s)
      松井敏高
    • Organizer
      第42回酸化反応討論会
    • Place of Presentation
      仙台
    • Year and Date
      2009-11-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] ベルドヘム-ヘムオキシゲナーゼ複合体の構造解析2009

    • Author(s)
      松井敏高, 大森宏平, 齋藤正男
    • Organizer
      第42回酸化反応討論会
    • Place of Presentation
      仙台
    • Year and Date
      2009-11-14
    • Related Report
      2011 Final Research Report
  • [Presentation] 構造を基にしたグルタミン酸受容体GluR5選択的化合物の設計2009

    • Author(s)
      海野昌喜, 篠原正将, 高山昴一郎, 渡邉朋子, 田中秀治, 酒井隆一, 佐々木誠, 齋藤正男
    • Organizer
      日本化学会関東支部茨城地区研究交流会
    • Place of Presentation
      日立
    • Year and Date
      2009-11-06
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 構造を基にしたグルタミン酸受容体GluR5選択的化合物の設計2009

    • Author(s)
      海野昌喜, 篠原正将, 高山昴一郎, 渡邉朋子, 田中秀治, 酒井隆一, 佐々木誠, 齋藤正男
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      兵庫県西宮市
    • Year and Date
      2009-10-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 構造を基にしたグルタミン酸受容体GluR5選択的化合物の設計2009

    • Author(s)
      海野昌喜
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structure of Heme Oxygenase Catalytic Intermediates2009

    • Author(s)
      齋藤正男
    • Organizer
      42nd IUPAC Congress
    • Place of Presentation
      グラスゴウ、イギリス
    • Year and Date
      2009-08-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structure of heme oxygenase catalytic intermediates2009

    • Author(s)
      M. Ikeda-Saito
    • Organizer
      42nd IUPAC Congress
    • Place of Presentation
      United Kingdom, Glasgow
    • Year and Date
      2009-08-02
    • Related Report
      2011 Final Research Report
  • [Presentation] Ring opening mechanism of verdoheme catalyzed by heme oxygenase2009

    • Author(s)
      T. Matsui, K. Omori, M. Ikeda-Saito
    • Organizer
      2nd International symposium on bioinorganic chemistry of the new era
    • Place of Presentation
      Japan, Takayama
    • Year and Date
      2009-08-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Ring Opening Mechanism of Verdoheme Catalyzed by Heme Oxygenase2009

    • Author(s)
      松井敏高
    • Organizer
      2nd International Symposium on Bioinorganic Chemistry of the New Era
    • Place of Presentation
      高山
    • Year and Date
      2009-07-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structure and catalytic mechanism of heme oxygenase2009

    • Author(s)
      M. Unno, T. Matsui, M. Ikeda-Saito
    • Organizer
      14th International conference on biological inorganic chemistry
    • Place of Presentation
      Japan, Nagoya
    • Year and Date
      2009-07-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural biological inorganic chemistry of heme oxygenase catalysis2009

    • Author(s)
      M. Ikeda-Saito, T. Matsui, M. Unno
    • Organizer
      14th International conference on biological inorganic chemistry
    • Place of Presentation
      Japan, Nagoya
    • Year and Date
      2009-07-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Biological Inorganic Chemistry of Heme Oxygenase Catalysis2009

    • Author(s)
      齋藤正男
    • Organizer
      第14回生物無機化学国際会議
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structure and Catalytic Mechanism of Heme Oxygenase2009

    • Author(s)
      海野昌喜
    • Organizer
      第14回生物無機化学国際会議
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Crystal structure of verdoheme. heme oxygenase complex : Implications for oxygen activation mechanism2009

    • Author(s)
      T. Matsui, K. Omori, M. Unno, M. Ikeda-Saito
    • Organizer
      14th International conference on biological inorganic chemistry
    • Place of Presentation
      Japan, Nagoya
    • Year and Date
      2009-07-25
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural insights into heme oxygenase catalysis2009

    • Author(s)
      M. Ikeda-Saito
    • Organizer
      34th Federation of european biochemical societies congress
    • Place of Presentation
      Czech Republic, Prague2
    • Year and Date
      2009-07-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insights into Heme Oxygenase Catalysis2009

    • Author(s)
      齋藤正男
    • Organizer
      34th Federation of European Biochemical Societies Congress
    • Place of Presentation
      プラハ、チェコ共和国
    • Year and Date
      2009-07-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] Crystal Structure of Verdoheme-Heme Oxygenase Complex : Implications for Oxygen Activation Mechanism2009

    • Author(s)
      松井敏高
    • Organizer
      第14回生物無機化学国際会議
    • Place of Presentation
      名古屋
    • Related Report
      2009 Annual Research Report
  • [Book] Nanohybridization of Organic-Inorganic Materials2009

    • Author(s)
      M. Unno, M. Ikeda-Saito
    • Publisher
      Springer
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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