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Paradigm shift in enzymatic heme degradation

Research Project

Project/Area Number 23550186
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemistry related to living body
Research InstitutionTohoku University

Principal Investigator

MATSUI Toshitaka  東北大学, 多元物質科学研究所, 准教授 (90323120)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsヘム代謝 / 酸素活性化 / 反応機構 / 病原性細菌 / ホルムアルデヒド / 結核菌 / 黄色ブドウ球菌 / 一酸化炭素 / ベルドヘム
Research Abstract

In this study, we have examined novel type reactions of enzymatic heme degradation. A recent in vitro study has revealed that a canonical heme degrading enzyme, heme oxygenase (HO), produces a new heme catabolite under special reaction condition. The new catabolite was successfully detected from mammalian cell culture, suggesting that the novel HO reaction can proceed in living organisms. On the other hand, newly-found IsdG-type enzymes degraded heme into unique reaction products through distinct reaction mechanisms. The mechanistic difference from the well-studied HO reaction appears to be caused by unusual non-planarity of heme bound to the IsdG-type enzymes. These diversity shed new light on enzymatic heme degradation to stimulate biological research exploring new physiological functions as well as its mechanistic studies.

Report

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

    (43 results)

All 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (32 results) (of which Invited: 7 results)

  • [Journal Article] 歪みで誘起される新たなヘム分解反応2014

    • Author(s)
      松井敏高
    • Journal Title

      生物物理

      Volume: 54 Pages: 104-105

    • NAID

      130003391409

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heme degradation by Staphylococcus aureus IsdG and IsdI liberates formaldehyde rather than carbon monoxide2013

    • Author(s)
      T. Matsui, S. Nambu, Y. Ono, C. W. Goulding, K. Tsumoto, M. Ikeda-Saito
    • Journal Title

      Biochemistry

      Volume: 52 Pages: 3025-3027

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new way to degrade heme : The Mycobacteriaum tuberoculosis enzyme MhuD catalyzes heme degradation without generating CO2013

    • Author(s)
      S. Nambu, T. Matsui, M., C. W. Goulding, S. Takahashi, M. Ikeda-Saito
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Pages: 10101-10109

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new way to degrade heme: The Mycobacterium tuberculosis enzyme MhuD catalyzes heme degradation without generating CO2013

    • Author(s)
      S. Nambu, T. Matsui, C. W. Goulding, S. Takahashi, M. Ikeda-Saito
    • Journal Title

      J. Biol. Chem.

      Volume: 印刷中 Issue: 14 Pages: 10101-10109

    • DOI

      10.1074/jbc.m112.448399

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crystallographic studies of heme oxygenase complexed with an unstable reaction intermediate, verdoheme2012

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

      J. Inorg. Biochem.

      Volume: 113 Pages: 102-109

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A heme degradation enzyme, HutZ, from Vibrio cholerae2012

    • Author(s)
      T. Uchida, Y. Sekine, T. Matsui, M. Ikeda- Saito, K. Ishimori
    • Journal Title

      Chem. Commun.

      Volume: 48 Pages: 6741-6743

    • NAID

      120006414019

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [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
      2013 Final Research Report 2011 Research-status 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
      2013 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
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] X-ray Crystallography of A Metalloprotein: A Reaction Intermediate of Heme Oxygenase2011

    • Author(s)
      海野昌喜, 他
    • Journal Title

      Nihon Kessho Gakkaishi

      Volume: 53 Issue: 3 Pages: 213-218

    • DOI

      10.5940/jcrsj.53.213

    • NAID

      10029371570

    • ISSN
      0369-4585, 1884-5576
    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oxygen Activation for the Heme Degradation: Utilization of Reactive Oxygen Species2011

    • Author(s)
      松井敏高
    • Journal Title

      Seibutsu Butsuri

      Volume: 51 Issue: 3 Pages: 132-133

    • DOI

      10.2142/biophys.51.132

    • NAID

      10029139987

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Unique reaction mechanisms of IsdG-type heme degrading enzymes from pathogenic bacteria2013

    • Author(s)
      T. Matsui
    • Organizer
      Sixth Korea-Japan Seminars on Biomolecular Sciences : Experiments and Simulations
    • Place of Presentation
      Japan, Okazaki
    • Year and Date
      2013-11-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Heme Degradation without Releasing CO : Unique Reaction Mechanism of IsdG-type Heme Degrading Enzymes2013

    • Author(s)
      T. Matsui, S. Nambu, Y. Ono, S. Takahashi, M. Ikeda-Saito C.W. Goulding K. Tsumoto
    • Organizer
      International Conference on BioInorganic Chemistry (ICBIC16)
    • Place of Presentation
      France, Grenoble
    • Year and Date
      2013-07-24
    • Related Report
      2013 Final Research Report
  • [Presentation] 歪みで誘起される新たなヘム代謝反応2013

    • Author(s)
      松井敏高
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Year and Date
      2013-06-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 新規IsdG型ヘム分解酵素の構造と反応機構2013

    • Author(s)
      松井敏高,南部周介,小野由香莉, C. W. Goulding,高橋聡,秋山公男,齋藤正男
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Year and Date
      2013-06-13
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘム代謝の多様な戦略2013

    • Author(s)
      松井敏高
    • Organizer
      分子研シンポジウム
    • Place of Presentation
      岡崎
    • Year and Date
      2013-06-01
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘム分解の多様な分子機構2013

    • Author(s)
      松井敏高
    • Organizer
      生物無機化学の新潮流と展望
    • Place of Presentation
      名古屋
    • Year and Date
      2013-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Heme Degradation without Releasing CO : Unique Reaction Mechanism of IsdG-type Heme Degrading Enzymes2013

    • Author(s)
      T. Matsui, S. Nambu, Y. Ono, C. W. Goulding, S. Takahashi, K. Tsumoto, M. Ikeda-Saito
    • Organizer
      NIH-Tohoku University-JSPS International Symposium on Cutting Edge Biomedical Research
    • Place of Presentation
      Japan, Sendai
    • Year and Date
      2013-05-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 結核菌由来ヘム分解酵素MhuDの活性中心構造と酵素活性2013

    • Author(s)
      南部周介,小野由香莉,松井敏高, C. W. Goulding,秋山公男,高橋聡,津本浩平,齋藤正男
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      草津
    • Year and Date
      2013-03-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 黄色ブドウ球菌由来IsdGにおける特殊なヘム分解生成物2013

    • Author(s)
      小野由香莉,南部周介,松井敏高, C. W. Goulding,高橋聡,津本浩平,齋藤正男
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      草津
    • Year and Date
      2013-03-22
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘムタンパク質におけるユニークな酸素活性化2013

    • Author(s)
      松井敏高
    • Organizer
      分子研研究会「生体配位化学の最前線と展望」
    • Place of Presentation
      岡崎
    • Year and Date
      2013-02-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 新規IsdG型ヘム分解酵素の構造と反応機構2012

    • Author(s)
      松井敏高,草間周介, C. W. Goulding,高橋聡,秋山公男,齋藤正男
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] IsdG型酵素による新規ヘム分解機構2012

    • Author(s)
      草間周介,松井敏高, C. W. Goulding,高橋聡,秋山公男,齋藤正男
    • Organizer
      第45回酸化反応討論会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] IsdG型酵素による新規ヘム分解機構2012

    • Author(s)
      草間周介,松井敏高, C. W. Goulding,高橋聡,秋山公男,齋藤正男
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-07
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘム分解の新たな戦略2012

    • Author(s)
      松井敏高
    • Organizer
      第11回化学系薬学若手セミナー
    • Place of Presentation
      仙台
    • Year and Date
      2012-09-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 結核菌由来ヘム分解酵素MhuDの活性中心構造と反応機構2012

    • Author(s)
      草間周介,松井敏高, C. W. Goulding,高橋聡,秋山公男,齋藤正男
    • Organizer
      第39回生体分子科学討論会
    • Place of Presentation
      仙台
    • Year and Date
      2012-06-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 新規IsdG型ヘム分解酵素の構造と反応機構2012

    • Author(s)
      松井敏高, 草間周介, C. W. Goulding, 高橋聡, 秋山公男, 齋藤正男
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 結核菌由来ヘム分解酵素MhuDの活性中心構造と反応機構2011

    • Author(s)
      草間周介,松井敏高, C. W. Goulding,秋山公男,高橋聡,齋藤正男
    • Organizer
      第44回酸化反応討論会
    • Place of Presentation
      吹田
    • Year and Date
      2011-11-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 結核菌由来ヘム分解酵素MhuDの活性中心構造と酵素活性2011

    • Author(s)
      草間周介,松井敏高, C. W. Goulding,秋山公男,高橋聡,齋藤正男
    • Organizer
      第38回生体分子科学討論会
    • Place of Presentation
      つくば
    • Year and Date
      2011-06-23
    • Related Report
      2013 Final 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
    • Related Report
      2013 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
    • Related Report
      2013 Final 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
    • Related Report
      2013 Final Research Report
  • [Presentation] Ring-opening mechanism of verdoheme by heme oxygenase2011

    • Author(s)
      T. Matsui, M. Ikeda-Saito
    • Organizer
      ICBIC 15-15th International Conference on Biological Inorganic Chemistry
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2011 Research-status Report
  • [Presentation] Heme Degradation without Releasing CO: Unique Reaction Mechanism of IsdG-type Heme Degrading Enzymes

    • Author(s)
      T. Matsui, S. Nambu, Y. Ono, C. W. Goulding, S. Takahashi, K. Tsumoto, M. Ikeda-Saito
    • Organizer
      NIH-Tohoku University-JSPS International Symposium on Cutting Edge Biomedical Research
    • Place of Presentation
      Sendai, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヘム分解の多様な分子機構

    • Author(s)
      松井敏高
    • Organizer
      生物無機化学の新潮流と展望
    • Place of Presentation
      名大(名古屋)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ヘム代謝の多様な戦略

    • Author(s)
      松井敏高
    • Organizer
      分子研シンポジウム2013
    • Place of Presentation
      分子研(岡崎)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 歪みで誘起される新たなヘム代謝反応

    • Author(s)
      松井敏高
    • Organizer
      第13回 日本蛋白質科学会年会
    • Place of Presentation
      とりぎん会館(鳥取)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Heme Degradation without Releasing CO: Unique Reaction Mechanism of IsdG-type Heme Degrading Enzymes

    • Author(s)
      T. Matsui, S. Nambu, Y. Ono, S. Takahashi, M. Ikeda-Saito C.W. Goulding K. Tsumoto
    • Organizer
      International Conference on BioInorganic Chemistry (ICBIC16)
    • Place of Presentation
      Grenoble, France
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Unique reaction mechanisms of IsdG-type heme dagrading enzymes from pathogenic bacteria

    • Author(s)
      T. Matsui
    • Organizer
      Sixth Korea-Japan Seminars on Biomolecular Sciences: Experiments and Simulations
    • Place of Presentation
      Okazaki, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ヘム分解の新たな戦略

    • Author(s)
      松井敏高
    • Organizer
      第11回化学系薬学若手セミナー
    • Place of Presentation
      東北大学
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] IsdG型酵素による新規ヘム分解機構

    • Author(s)
      草間周介, 松井敏高, Celia W. Goulding, 高橋聡, 秋山公男, 齋藤正男
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学
    • Related Report
      2012 Research-status Report
  • [Presentation] IsdG型酵素による新規ヘム分解機構

    • Author(s)
      草間周介, 松井敏高, Celia W. Goulding, 高橋聡, 秋山公男, 齋藤正男
    • Organizer
      第45回酸化反応討論会
    • Place of Presentation
      名古屋市立大学
    • Related Report
      2012 Research-status Report
  • [Presentation] ヘムタンパク質におけるユニークな酸素活性化

    • Author(s)
      松井敏高
    • Organizer
      分子研研究会「生体配位化学の最前線と展望」
    • Place of Presentation
      分子科学研究所
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2011-08-05   Modified: 2019-07-29  

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