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Investigation of the mechanism of heme degradation by heme oxygenase-1

Research Project

Project/Area Number 19750150
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Chemistry related to living body
Research InstitutionKurume University

Principal Investigator

SATO Hideaki  Kurume University, 医学部, 准教授 (60271996)

Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,440,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥540,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsヘム代謝 / 酵素反応機構 / 酸化還元電位 / 構造生物学 / 生体分子 / 酵素反応 / 生物物理
Research Abstract

Heme oxygenase (HO) catalyses the degradation of heme via three successive monooxygenase reactions. To probe the cleavage mechanism of oxaporphyrin ring of ferrous a-verdoheme, an intermediate in the HO reaction, ferrous verdoheme-rat HO-1 complex was prepared under anaerobic conditions. Electrochemical reduction of the complex was performed under anaerobic conditions and the reduction potential for one-electron reduction of the oxaporphyrin ring of ferrous verdoheme was determined. Effects of ligands such as CO on the electrochemical reduction and the electron transfer from NADPH-cytochrome P450 reductase to the complex were investigated. In addition, the crystal structure of rat HO-1 in complex with ferrous a -verdoheme was determined. On the basis of results in these experiments, the degradation mechanism of ferrous verdoheme under the physiological condition has discussed.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (40 results)

All 2010 2009 2008 2007 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (29 results) Remarks (1 results)

  • [Journal Article] Crystal Structure of Rat Haem Oxygenase-1 in Complex with Ferrous Verdohaem: Presence of a Hydrogen-Bond Network on the Distal Side2009

    • Author(s)
      Hideaki Sato, Masakazu Sugishima, Hiroshi Sakamoto, Yuichiro Higashimoto, Chizu Shimokawa, Keiichi Fukuyama, Graham Palmer, Masato Noguchi
    • Journal Title

      Biochem. J. 419

      Pages: 339-345

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Metals in Enzymatic and Nonenzymatic Decomposition of C-Terminalα- Hydroxyglycine to Amide: An Implication for the Catalytic Role of Enzyme-Bound Zinc in the Peptidylamidoglycolate Lyase Reaction2009

    • Author(s)
      Kenichi Takahashi, Saori Harada, Yuichiro Higashimoto, Chizu Shimokawa, Hideaki Sato, Masakazu Sugishima, Yasuhiko Kaida, Masato Noguchi
    • Journal Title

      Biochemistry 48

      Pages: 1654-1662

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal Structure of Rat Haem Oxygenase-1 in Complex with Ferrous Verdohaem : Presence of a Hydrogen-Bond Network on the Distal Side2009

    • Author(s)
      Hideaki Sato, Masakazu Sugishima, Hiroshi Sakamoto, Yuichiro Higashimoto, Chizu Shimokawa, Keiichi Fukuyama, Graham Palmer, Masato Noguchi
    • Journal Title

      Biochemical Journal 419

      Pages: 339-345

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Metals in Enzymatic and Nonenzymatic Decomposition of C-Terminal α-Hydroxyglycine to Amide : An Implication for the Catalytic Role of Enzyme-Bound Zinc in the Peptidylamidoglycolate Lyase Reaction2009

    • Author(s)
      Kenichi Takahashi, Saori Harada, Yuichiro Higashimoto, Chizu Shimokawa, Hideaki Sato, Masakazu Sugishima, Yasuhiko Kaida, Masato Noguchi
    • Journal Title

      Biochemistry 48

      Pages: 1654-1662

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mass Spectrometric Identification of Lysine Residues of Heme Oxygenase-1 That Are Involved in Its Interaction with NADPH-cytochrome P450 Reductase2008

    • Author(s)
      Yuichiro Higashimoto, Masakazu Sugishima, Hideaki Sato, Hiroshi Sakamoto, Keiichi Fukuyama, Graham Palmer, Masato Noguchi
    • Journal Title

      Biochem. Biophys. Res. Commun. 367

      Pages: 852-858

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mass Spectrometric Identification of Lysine Residues of Heme Oxygenase-1 That Are Involved in Its Interaction with NADPH-Cytochrome P450 Reductase2008

    • Author(s)
      Yuichiro Higashimoto, Masakazu Sugishima, Hideaki Sato, Hiroshi Sakamoto, Keiichi Fukuyama, Graham Palmer, Masato Noguchi
    • Journal Title

      Biochemical and Biophysical Research Communications 367

      Pages: 852-858

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemical Reduction of Ferrousα-Verdoheme in Complex with Heme Oxygenase-12007

    • Author(s)
      Hideaki Sato, Yuichiro Higashimoto, Hiroshi Sakamoto, Masakazu Sugishima, Kenichi Takahashi, Graham Palmer, Masato Noguchi
    • Journal Title

      J. Inorg. Biochem. 101

      Pages: 1394-1399

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Supramolecular Hemoprotein Linear Assembly by Successive Interprotein Heme-Heme Pocket Interactions2007

    • Author(s)
      Hiroaki Kitagishi, Koji Oohora, Hiroyasu Yamaguchi, Hideaki Sato, Takashi Matsuo, Akira Harada, Takashi Hayashi
    • Journal Title

      J. Am. Chem. Soc. 129

      Pages: 10326-10327

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemical Reduction of Ferrous α-Verdoheme in Complex with Heme Oxygenase-12007

    • Author(s)
      Hideaki Sato, Yuichiro Higashimoto, Hiroshi Sakamoto, Masakazu Sugishima, Kenichi Takahashi, Graham Palmer, Masato Noguchi
    • Journal Title

      Journal of Inorganic Biochemistry 101

      Pages: 1394-1399

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Supramolecular Hemoprotein Linear Assembly by Successive Interprotein Heme-Heme Pocket Interactions2007

    • Author(s)
      Hiroaki Kitagishi, Koji Oohora, Hiroyasu Yamaguchi, Hideaki Sato, Takashi Matsuo, Akira Harada, Takashi Hayashi
    • Journal Title

      Journal of the American Chemical Society 129

      Pages: 10326-10327

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] ベルドヘム-ヘムオキシゲナーゼ-1複合体の構造解析(Crystal structure of verdoheme-heme oxygenase-1 complex)2010

    • Author(s)
      佐藤透盟, 杉島正一, 坂本寛, 東元祐一郎, 福山恵一, 野口正人
    • Organizer
      日本化学会第90春季年会
    • Place of Presentation
      東大阪
    • Year and Date
      2010-03-29
    • Related Report
      2009 Final Research Report
  • [Presentation] ベルドヘム-ヘムオキシゲナーゼ-1複合体の構造解析(Crystal structure of verdoheme-heme oxygenase-1 complex)2010

    • Author(s)
      佐藤秀明, 杉島正一, 坂本寛, 東元祐一郎, 福山恵一, 野口正人
    • Organizer
      日本化学会第90春季年会
    • Place of Presentation
      近畿大学(東大阪市)
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] ペプチドアミド化反応における亜鉛および鉄イオンの役割(The roles of zinc and iron ion in peptide amidation)2010

    • Author(s)
      下川千寿, 原田沙織, 東元祐一郎, 佐壷透盟, 杉島正一, 野口正人
    • Organizer
      日本化学会第90春季年会
    • Place of Presentation
      東大阪
    • Year and Date
      2010-03-28
    • Related Report
      2009 Final Research Report
  • [Presentation] ペプチドアミド化反応における亜鉛および鉄イオンの役割(The roles of zinc and iron ion in peptide amidation)2010

    • Author(s)
      下川千寿, 原田沙織, 東元祐一郎, 佐藤秀男, 杉島正一, 野口正人
    • Organizer
      日本化学会第90春季年会
    • Place of Presentation
      近畿大学(東大阪市)
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] Ferrousα-Verdoheme in Complex with Rat Heme Oxygenase-12009

    • Author(s)
      Hideaki Sato, Masakazu Sugishima, Yuichiro Higashimoto, Hiroshi Sakamoto, Chizu Shimokawa, Masato Noguchi
    • Organizer
      Its Crystal Structure and Electrochemistry (The 6th International Congress on Heme Oxygenases: Heme Oxygenases in Biology and Medicine
    • Place of Presentation
      Miami Beach, Florida, U.S.A.
    • Year and Date
      2009-10-02
    • Related Report
      2009 Final Research Report
  • [Presentation] Ferrous α-Verdoheme in Complex with Rat Heme Oxygenase-1. Its Crystal Structure and Electrochemistry2009

    • Author(s)
      Hideaki Sato, Masakazu Sugishima, Yuichiro Higashimoto, Hiroshi Sakamoto, Chizu Shimokawa, Masato Noguchi
    • Organizer
      The 6th International Congress on Heme Oxygenases : Heme Oxygenases in Biology and Medicine
    • Place of Presentation
      Miami Beach, Florida, U.S.A.
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] α-ベルドヘム-ヘムオキシゲナーゼ-1複合体の電気化学と結晶構造2009

    • Author(s)
      佐藤秀明, 杉島正一, 東元祐一郎, 坂本寛, 福山恵一, 野口正人
    • Organizer
      第24回生体機能関連化学シンポジウム・第12回バイオテクノロジー部会シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2009-09-14
    • Related Report
      2009 Final Research Report
  • [Presentation] Peptidylamidoglycolate lyase反応における鉄および亜鉛イオンの役割2009

    • Author(s)
      下川千寿, 原田沙織, 東元祐一郎, 佐藤秀明, 杉島正一, 野口正人
    • Organizer
      第24回生体機能関連化学シンポジウム・第12回バイオテクノロジー部会シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2009-09-14
    • Related Report
      2009 Final Research Report
  • [Presentation] α-ベルドヘム-ヘムオキシゲナーゼ-1複合体の電気化学と結晶構造2009

    • Author(s)
      佐藤秀明, 杉島正一, 東元祐一郎, 坂本寛, 福山恵一, 野口正人
    • Organizer
      第24回生体機能関連化学シンポジウム・第12回バイオテクノロジー部会シンポジウム
    • Place of Presentation
      九州大学(福岡市)
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] Peptidylamidoglycolate lyase 反応における鉄および亜鉛イオンの役割2009

    • Author(s)
      下川千寿, 原田沙織, 東元祐一郎, 佐藤秀明, 杉島正一, 野口正人
    • Organizer
      第24回生体機能関連化学シンポジウム・第12回バイオテクノロジー部会シンポジウム
    • Place of Presentation
      九州大学(福岡市)
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] α-ベルドヘム-ヘムオキシゲナーゼ-1複合体の結晶構造2009

    • Author(s)
      佐藤秀明, 杉島正一, 坂本寛, 東元祐一郎, 野口正人
    • Organizer
      平成21年度日本生化学会九州支部例会
    • Place of Presentation
      福岡
    • Year and Date
      2009-05-17
    • Related Report
      2009 Final Research Report
  • [Presentation] α-ベルドヘム-ヘムオキシゲナーゼ-1複合体の結晶構造2009

    • Author(s)
      佐藤秀明, 杉島正一, 坂本寛, 東元祐一郎, 野口正人
    • Organizer
      平成21年度日本生化学会九州支部例会
    • Place of Presentation
      九州大学(福岡市)
    • Year and Date
      2009-05-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] ベルドヘム-ヘムオキシゲナーゼ-1複合体の還元反応2009

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 杉島正一, 野口正人
    • Organizer
      日本化学会第89春季年会
    • Place of Presentation
      船橋
    • Year and Date
      2009-03-29
    • Related Report
      2009 Final Research Report
  • [Presentation] ベルドヘムーヘムオキシゲナーゼ-1複合体の還元反応(Reduction of verdoheme-heme oxygenase-1 complex)2009

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 杉島正一, 野口正人
    • Organizer
      日本化学会第89春季年会
    • Place of Presentation
      船橋市
    • Year and Date
      2009-03-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] 質量分析法によるヘムオキシゲナーゼとNADPH-シトクロムP450還元酵素, ビリベルジン還元酵素との相互作用解析2008

    • Author(s)
      東元祐一郎, 杉島正一, 佐藤秀明, 下川千寿, 原田沙織, 坂本寛, 野口正人
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2009 Final Research Report
  • [Presentation] CO配位型ベルドヘム-ヘムオキシゲナーゼ複合体のオキサポルフィリン環の還元2008

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 杉島正一, 下川千寿, 原田沙織, 野口正人
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2009 Final Research Report
  • [Presentation] Crystal Structure of Rat Verdoheme-Heme Oxygenase-1 Complex2008

    • Author(s)
      Masakazu Sugishima, Hideaki Sato, Yuichiro Higashimoto, Hiroshi Sakamoto, Chizu Shimokawa, Saori Harada, Keiichi Fukuyama, Masato Noguchi
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2009 Final Research Report
  • [Presentation] 質量分析法によるヘムオキシゲナーゼとNADPH-シトクロムP450還元酵素, ビリベルジン還元酵素との相互作用解析2008

    • Author(s)
      東元祐一郎, 杉島正一, 佐藤秀明, 下川千寿, 原田沙織, 坂本寛, 野口正人
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸市
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] CO配位型ベルドヘムーヘムオキシゲナーゼ複合体の オキサポルフィリン環の還元(Reduction of oxaporphyrin ring of CO-bound verdoheme-heme oxygenase complex)2008

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 杉島正一, 下川千寿, 原田沙織, 野口正人
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸市
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Crystal Structure of Rat Verdoheme-Heme Oxygenase-1 Complex2008

    • Author(s)
      Masakazu Sugishima, Hideaki Sato, Yuichiro Higashimoto, Hiroshi Sakamoto, Chizu Shimokawa, Saori Harada, Keiichi Fukuyama, Masato Noguchi
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸市
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 質量分析法によるヘムオキシゲナーゼとNADPH-シトクロムP450還元酵素, ビリベルジン還元酵素との相互作用解析2008

    • Author(s)
      東元祐一郎, 杉島正一, 佐藤秀明, 坂本寛, 野口正人
    • Organizer
      平成20年度日本生化学会九州支部例会
    • Place of Presentation
      福岡
    • Year and Date
      2008-05-18
    • Related Report
      2009 Final Research Report
  • [Presentation] 質量分析法によるヘムオキシゲナーゼとNADPH-シトクロムP450還元酵素,ビリベルジン還元酵素との相互作用解析2008

    • Author(s)
      東元祐一郎, 杉島正一, 佐藤秀明, 坂本寛, 野口正人
    • Organizer
      平成20年度日本生化学会九州支部例会
    • Place of Presentation
      福岡市
    • Year and Date
      2008-05-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] 共鳴ラマン分光法によるインドールアミン2, 3ジオキシゲナーゼの解析(Analysis of substrate interaction of human indoleamine 2, 3-dioxygenase by resonance Raman spectroscopy and site-directed mutagenesis)2007

    • Author(s)
      四ッ谷景子, 杉本宏, 大槻崇史, 佐藤秀明, 吉田匡, 小倉尚志, 城宜嗣
    • Organizer
      第45回日本生物物理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-23
    • Related Report
      2009 Final Research Report
  • [Presentation] α-ベルドヘム-ラットヘムオキシゲナーゼ-1複合体の電気化学的還元(Electrochemical reduction of ferrous a -verdoheme-rat heme oxygenase-1 complex)2007

    • Author(s)
      佐藤秀盟, 東元祐一郎, 坂本寛, 野口正人
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会(BMB2007)
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2009 Final Research Report
  • [Presentation] α-ベルドヘムーラットヘムオキシゲナーゼー1複合体の電気化学的還元(Electrochemical Reduction of Ferrous α-Verdoheme-Rat Heme Oxygenase-1 Complex)2007

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 野口正人
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会(BMB2007)
    • Place of Presentation
      横浜市
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] FMN欠失NADPH-シトクロムP450還元酵素を用いたヘムオキシゲナーゼ反応における電子授受機構の検討2007

    • Author(s)
      東元祐一郎, 佐藤秀盟, 杉島正一, 坂本寛, 野口正人
    • Organizer
      第7回日本蛋白質科学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2007-05-25
    • Related Report
      2009 Final Research Report
  • [Presentation] FMN欠失NADPH-シトクロムP450還元酵素を用いたヘムオキシゲナーゼ反応における電子授受機構の検討2007

    • Author(s)
      東元祐一郎, 佐藤秀明, 杉島正一, 坂本寛, 野口正人
    • Organizer
      第7回日本蛋白質科学会年会
    • Place of Presentation
      仙台市
    • Year and Date
      2007-05-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] ベルドヘム-ヘムオキシゲナーゼ複合体の電気化学的還元2007

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 野口正人
    • Organizer
      平成19年度日本生化学会九州支部例会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-05-19
    • Related Report
      2009 Final Research Report
  • [Presentation] ベルドヘムーヘムオキシゲナーゼ複合体の電気化学的還元2007

    • Author(s)
      佐藤秀明, 東元祐一郎, 坂本寛, 野口正人
    • Organizer
      平成19年度日本生化学会九州支部例会
    • Place of Presentation
      宮崎市
    • Year and Date
      2007-05-19
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://gmed.kurume-u.ac.jp/rink/index3.html

    • Related Report
      2009 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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