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Emergence of novel functions through integration of bio-metal complexes with nucleic acids and its application to integrated bio-metal science

Publicly Offered Research

Project AreaIntegrated Biometal Science: Research to Explore Dynamics of Metals in Cellular System
Project/Area Number 20H05496
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionUniversity of Tsukuba

Principal Investigator

山本 泰彦  筑波大学, 数理物質系, 教授 (00191453)

Project Period (FY) 2020-10-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords四重鎖DNA / ヘム / G-カルテット / 酸化触媒作用 / キラターゼ活性 / 核酸酵素 / 四重鎖核酸 / 機能創発 / RNAワールド / 生命の誕生 / 四重鎖RNA / U-カルテット / 金属付加酵素 / 機能性核酸 / 触媒機構
Outline of Research at the Start

リボザイムの発見は、原始地球上における前生物進化で存在していたと考えられている「RNAワールド」仮説の根拠の一つとして知られている。ただし、現在知られているリボザイムは、加水分解反応に対する触媒活性を示すRNAのみであるので、「RNAワールド」における自己複製系の実現には不十分である。生命の起源に迫るためには、多様な機能を示すリボザイムを新しいアプローチで探索する研究が必要である。本研究では、原始地球上で存在していた可能性があるテトラピロール類と生命金属の錯体を補欠分子族として四重鎖RNAに組込むことにより、生命誕生の鍵となる触媒活性を示すリボザイムを創製する。

Outline of Annual Research Achievements

私は、生物界に遍在する四重鎖核酸とヘムの相互作用の理解は、生命誕生、さらには生物進化を理解する上で、重要な鍵になると考えている。今年度は、四重鎖DNAが環状テトラピロール類への金属イオン挿入反応を促進する酵素キラターゼとして作用する可能性を検討する研究、そしてヘムと四重鎖DNAの複合体が示す触媒活性の発現機構を解明する研究を行った。
ヘムの生合成では、最終段階でポルフィリン環へのFe2+の挿入が起こる。この反応は遅いので、生体内では酵素が存在する。私は、プロトポルフィリンⅨ (PPIX)へのCu2+挿入反応に対する四重鎖DNAのキラターゼ活性を解析した。まず、NMRにより、PPIXは四重鎖DNAの3’末端G-カルテットに特異的に結合することを明らかにした。そして、PPIXに10当量の四重鎖DNAを添加すると、Cu2+挿入反応の初速度が約30倍増大することを明らかにし、四重鎖DNAのキラターゼ活性を実証することに成功した。PPIXとG-カルテットの接触界面において、G-カルテット中央の電子豊富なカルボニル酸素原子にCu2+が結合することで、その後のPPIXへの配位に必要な複数の反応が促進されたと考えられる。
ヘムは、四重鎖DNAの3’末端G-カルテットに特異的に結合し、酸化触媒活性をもつ複合体を形成する。これまでの研究から、複合体の酸化触媒活性の発現には、軸配位子としてヘム鉄に結合する水分子が重要な役割を担っていることが推測されている。私は、複合体の反応性の調節に重要だと考えられている当該水分子に由来する1H NMRシグナルの観測に成功した。さらに、当該水分子の電子的性質を明らかにすると共に、ヘム鉄を介した当該水分子とヘムの電子的相互作用の検出にも成功した。当該水分子の性質の解明を通して、G-カルテットに結合したヘムが示す触媒活性の発現機構の解明が飛躍的に進むことが期待される。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (33 results)

All 2022 2021 2020 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (22 results) (of which Int'l Joint Research: 13 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Nature of a H2O Molecule Confined in the Hydrophobic Interface between the Heme and G-Quartet Planes in a Heme-DNA Complex2022

    • Author(s)
      Nakajima Yusuke、Momotake Atsuya、Suzuki Akihiro、Neya Saburo、Yamamoto Yasuhiko
    • Journal Title

      Biochemistry

      Volume: - Issue: 7 Pages: 523-534

    • DOI

      10.1021/acs.biochem.1c00751

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Heme Electronic Structure and Local Heme Environment on Catalytic Activity of a Peroxidase-Mimicking Heme-DNAzyme2021

    • Author(s)
      Hagiwara Shota、Momotake Atsuya、Ogura Takashi、Yanagisawa Sachiko、Suzuki Akihiro、Neya Saburo、Yamamoto Yasuhiko
    • Journal Title

      Inorganic Chemistry

      Volume: 60 Issue: 15 Pages: 11206-11213

    • DOI

      10.1021/acs.inorgchem.1c01179

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular recognition of G-quadruplex DNA by Pheophorbide a2021

    • Author(s)
      Okamoto China、Momotake Atsuya、Kobayashi Masami、Yamamoto Yasuhiko
    • Journal Title

      Chemistry Letters

      Volume: - Issue: 6 Pages: 1278-1281

    • DOI

      10.1246/cl.210130

    • NAID

      130008053396

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A cationic copolymer as a cocatalyst for a peroxidase-mimicking heme-DNAzyme2021

    • Author(s)
      Araki Haruka、Hagiwara Shota、Shinomiya Ryosuke、Momotake Atsuya、Kotani Hiroaki、Kojima Takahiko、Ochiai Takuro、Shimada Naohiko、Maruyama Atsushi、Yamamoto Yasuhiko
    • Journal Title

      Biomaterials Science

      Volume: 9 Issue: 18 Pages: 6142-6152

    • DOI

      10.1039/d1bm00949d

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural and functional characterization of complexes between heme and dimeric parallel G-quadruplex DNAs2021

    • Author(s)
      Okamoto China、Momotake Atsuya、Yamamoto Yasuhiko
    • Journal Title

      Journal of Inorganic Biochemistry

      Volume: 216 Pages: 111336-111336

    • DOI

      10.1016/j.jinorgbio.2020.111336

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photogeneration of Reactive Oxygen Species from Water-Soluble Phthalocyanine Derivatives Bound to a G-Quadruplex DNA2020

    • Author(s)
      Uchiyama Mami、Momotake Atsuya、Ikeue Takahisa、Yamamoto Yasuhiko
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 93 Issue: 12 Pages: 1504-1508

    • DOI

      10.1246/bcsj.20200178

    • NAID

      130007955892

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of the Electron Density of the Heme Fe Atom on the Nature of Fe-O2 Bonding in Oxy Myoglobin2020

    • Author(s)
      Yamamoto Yasuhiko、Hasegawa Kazuyasu、Shibata Tomokazu、Momotake Atsuya、Ogura Takashi、Yanagisawa Sachiko、Neya Saburo、Suzuki Akihiro、Kobayashi Yasuhiro、Saito Makina、Seto Makoto、Ohta Takehiro
    • Journal Title

      Inorganic Chemistry

      Volume: 60 Issue: 2 Pages: 1021-1027

    • DOI

      10.1021/acs.inorgchem.0c03123

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stepwise binding of a cationic phthalocyanine derivative to an all parallel-stranded tetrameric G-quadruplex DNA2020

    • Author(s)
      Uchiyama Mami、Okamoto China、Momotake Atsuya、Ikeue Takahisa、Yamamoto Yasuhiko
    • Journal Title

      Journal of Inorganic Biochemistry

      Volume: 213 Pages: 111270-111270

    • DOI

      10.1016/j.jinorgbio.2020.111270

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 四重鎖DNAのキラターゼ活性2022

    • Author(s)
      鳥越果林,岡本千奈,百武篤也,山本泰彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] フェオホルバイドaとグアニン四重鎖DNAの相互作用2022

    • Author(s)
      岡本千奈,百武篤也,小林正美,山本泰彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヘム-DNA酵素におけるヘムとG-カルテットの接触界面に存在する水分子の解析2022

    • Author(s)
      中島優輔,百武篤也,鈴木秋弘,根矢三郎,山本泰彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] アニオン性フタロシアニン-四重鎖DNA複合体の解析2022

    • Author(s)
      小田原佑典,百武篤也,山本泰彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 熱安定性が高いヘム-DNA酵素のペルオキシダーゼ活性の解析2022

    • Author(s)
      深澤大輝,百武篤也,山本泰彦
    • Organizer
      日本化学会第102春季年会(2022)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Characterization of a Complex Between Heme(Fe3+) and a G-quadruplex DNA2021

    • Author(s)
      Y. Nakajima, S. Neya, A. Suzuki, A. Momotake, and Y. Yamamoto
    • Organizer
      Joint Conference of 22nd ISMAR, 9th APNMR, 60th NMRSJ(2021), and 60th SEST
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular Recognition of G-Quadruplex DNAs by Tetrapyrrole Macrocyclic Ligands2021

    • Author(s)
      C. Okamoto, A. Momotake, and Y. Yamamoto
    • Organizer
      Joint Conference of 22nd ISMAR, 9th APNMR, 60th NMRSJ(2021), and 60th SEST
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of Myoglobins Where Exogenous Ligands Replace the Proximal Histidine2021

    • Author(s)
      R. Murata, T. Sugita, T. Matsuo, S. Hirota, S. Yanagisawa, S. Neya, A. Suzuki, O. Shoji, Y. Watanabe, A. Momotake, and Y. Yamamoto
    • Organizer
      Joint Conference of 22nd ISMAR, 9th APNMR, 60th NMRSJ(2021), and 60th SEST
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Heme Electronic Structure and Local Heme Environment of a Peroxidase-Mimicking Heme-DNAzyme2021

    • Author(s)
      S. Hagiwara, A. Sugahara, R. Shinomiya, S. Neya, A. Suzuki, A. Momotake, and Y. Yamamoto
    • Organizer
      Joint Conference of 22nd ISMAR, 9th APNMR, 60th NMRSJ(2021), and 60th SEST
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interaction between Heme and Non-Standard Base Inosine(I)-Quartet2021

    • Author(s)
      A. Momotake, A. Sugahara, K. Torigoe, Y. Nakajima, S. Neya, A. Suzuki, and Y. Yamamoto
    • Organizer
      Joint Conference of 22nd ISMAR, 9th APNMR, 60th NMRSJ(2021), and 60th SEST
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interaction between Zn(II) Phthalocyanine Derivatives and a G-Quadruplex DNA2021

    • Author(s)
      S. Homma, M. Uchiyama, A. Momotake, T. Ikeue, and Y. Yamamoto
    • Organizer
      Joint Conference of 22nd ISMAR, 9th APNMR, 60th NMRSJ(2021), and 60th SEST
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of the Regulatory Mechanism for Peroxidase Activity of DNAzyme Possessing Heme2021

    • Author(s)
      S. Hagiwara, R. Shinomiya, A. Momotake, S. Neya, A. Suzuki, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of a Complex Consisting of Paramagnetic Heme(Fe3+) and G-Guadruplex DNA Formed from d(TAGGGTGGGTTGGGTGIG)2021

    • Author(s)
      Y. Nakajima, S. Neya, A. Suzuki, A. Momotake, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study of Myoglobin Reconstituted with a Chemically-Modified Heme Cofactor Possessing a Trifluoro Methyl Group at 5-Meso Position2021

    • Author(s)
      R. Murata, A. Momotake, A. Suzuki, T. Matsuo, S. Hirota, S. Neya, M. Senda, T. Senda, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interaction between Heme and I-quartet in a Heme-DNAzyme2021

    • Author(s)
      T. Torigoe, A. Momotake, S. Neya, S. Yanagisawa, T. Ogura, A. Suzuki, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study on the Effect of G-Quadruplex DNA on Photochemical Behaviors of Cationic Phthalocyanine Derivatives2021

    • Author(s)
      M. Uchiyama, A. Momotake, T. Ikeue, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular Recognition of G-Quadruplex DNA by Pheophorbide a2021

    • Author(s)
      C. Okamoto, A. Momotake, M. Kobayashi, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interaction of Cationic Phthalocyanine Derivatives with Guanine Nucleobases2021

    • Author(s)
      S. Homma, M. Uchiyama, A. Momotake, T. Ikeue, and Y. Yamamoto
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生命金属錯体と核酸の組織化による機能創発と生命金属元素戦略解明への応用2021

    • Author(s)
      山本泰彦
    • Organizer
      新学術領域研究「生命金属科学」領域会議 第四回地方巡業(東京)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Interaction between Tetrapyrrole Macrocycles and Quadruplex Nucleic Acids2021

    • Author(s)
      Y. Yamamoto
    • Organizer
      60th Annual Meeting of the Nuclear Magnetic Resonance Society of Japan (2021)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生命金属錯体と核酸の組織化による機能創発と生命金属元素戦略解明への応用2021

    • Author(s)
      山本泰彦
    • Organizer
      生命金属科学 ルスツ夏合宿
    • Related Report
      2021 Annual Research Report
  • [Presentation] 四重鎖 DNA とフタロシアニン誘導体の複合体の解析2020

    • Author(s)
      内山真見、岡本千奈、百武篤也、山本泰彦、池上崇久
    • Organizer
      第59回NMR討論会(2020)
    • Related Report
      2020 Annual Research Report
  • [Book] 核酸科学ハンドブック2020

    • Author(s)
      日本核酸化学会監、杉本 直己編
    • Total Pages
      576
    • Publisher
      講談社
    • ISBN
      9784065207864
    • Related Report
      2020 Annual Research Report
  • [Remarks] 筑波大学 数理物質系 生物無機化学研究室

    • URL

      https://www.chem.tsukuba.ac.jp/yamamoto/gyouseki.php

    • Related Report
      2021 Annual Research Report
  • [Remarks] 筑波大学 数理物質系 生物無機化学研究室

    • URL

      http://www.chem.tsukuba.ac.jp/yamamoto/

    • Related Report
      2020 Annual Research Report

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Published: 2020-11-04   Modified: 2022-12-28  

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