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Identification of novel antibacterial compound produced by artificial prenyltransferase.

Research Project

Project/Area Number 17KK0141
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionKitasato University (2019-2020)
Tohoku University (2017-2018)

Principal Investigator

Matsui Takashi  北里大学, 理学部, 講師 (30463582)

Project Period (FY) 2018 – 2020
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
KeywordsFtsZ / プレニル基転移酵素 / 電子顕微鏡 / LC-MS / 生合成酵素 / LC-MS/MS / タンパク質相互作用 / 質量分析計 / クライオ電子顕微鏡 / 単粒子構造解析 / 抗生物質
Outline of Final Research Achievements

Some secondary metabolites derived from Streptomyces show a wide variety of the biological activity, such as antiparasitic and antitumor. During a previous project, we got novel compounds produced by artificial enzymes based on indole prenyltransferase. In the other project, we determined the complex crystal structure of FtsZ, which is a critical role for bacterial cell division, with compound and revealed its inhibitory mechanism as well. Therefore, in this study, to evaluate the anti-FtsZ activity of the novel compounds, we used electron microscopy and LC-MS/MS, resulting that we developed a novel measurement procedure for identification of protein state using LC-MS/MS.

Academic Significance and Societal Importance of the Research Achievements

細菌の細胞分裂に関与するFtsZは、既存の細菌感染症治療ターゲットと異なることから、新規標的分子として注目されている。代表者の先行研究ではFtsZに対する阻害活性分子の阻害活性機序を明らかにし、また、人工酵素による機能性化合物も創出してきた。そこで、本研究では、新規創出化合物からFtsZの活性を阻害する分子の探索系の確立を目指した。その結果、標的蛋白質分子の構造様式の変化を検出を可能とする測定・解析手法を確立できた。今後は、細胞分裂過程で立体構造変化を生じるFtsZに対し化合物を添加することで構造様式がどのように促進・抑制・変化するか検出し、さらなる阻害分子の導出と阻害機序の解明を目指す。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (30 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (10 results) Book (1 results) Remarks (9 results)

  • [Int'l Joint Research] Max-Planck Institute of Molecular Physiology(ドイツ)2018

    • Year and Date
      2018-08-13
    • Related Report
      2020 Annual Research Report
  • [Journal Article] A highly efficient method for extracting peptides from a single mouse hypothalamus2021

    • Author(s)
      Yuzuru Nakagawa, Takashi Matsui, Ryo Konno, Yusuke Kawashima, Toshiya Sato, Makoto Itakura, Yoshio Kodera
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 548 Pages: 155-160

    • DOI

      10.1016/j.bbrc.2021.02.041

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Highly accurate and precise quantification strategy using stable isotope dimethyl labeling coupled with GeLC-MS/MS2021

    • Author(s)
      Ryo Konno, Takashi Matsui, Hiroaki Ito, Yusuke Kawashima, Makoto Itakura, Yoshio Kodera
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 550 Pages: 37-42

    • DOI

      10.1016/j.bbrc.2021.02.101

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional reconstruction of 3.8 MDa respiratory protein complex Hemocyanin2020

    • Author(s)
      松井 崇、加藤 早苗、田中 良和
    • Journal Title

      生化学

      Volume: 92 Issue: 1 Pages: 113-119

    • DOI

      10.14952/SEIKAGAKU.2020.920113

    • NAID

      40022176183

    • ISSN
      0037-1017
    • Year and Date
      2020-02-25
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cryo-EM Analysis Reveals the Asymmetric Assembly of the <i>Todarodes pacificus</i> Hemocyanin(TpH)2019

    • Author(s)
      松井 崇、加藤 早苗、田中 良和
    • Journal Title

      Nihon Kessho Gakkaishi

      Volume: 61 Issue: 4 Pages: 211-212

    • DOI

      10.5940/jcrsj.61.211

    • NAID

      130007761354

    • ISSN
      0369-4585, 1884-5576
    • Year and Date
      2019-12-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein encapsulation in the hollow space of hemocyanin crystals containing a covalently conjugated ligand2019

    • Author(s)
      Tsubasa Hashimoto, Yuxin Ye, Mihoko Ui, Tohohisa Ogawa, Takashi Matsui, and Yoshikazu Tanaka
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 印刷中 Issue: 1 Pages: 31-36

    • DOI

      10.1016/j.bbrc.2019.04.062

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the catalytic unit of GH87-type α-1,3-glucanase Agl-KA from Bacillus circulans2019

    • Author(s)
      S. Yano, W. Suyotha, N. Oruro, T. Matsui, S. Shiga, T. Itoh, T. Hibi, Y. Tanaka, M. Wakayama, K. Makabe
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 15259-15259

    • DOI

      10.1038/s41598-019-51822-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Encapsulation of biomacromolecules by soaking and co-crystallization into porous protein crystals of hemocyanin2019

    • Author(s)
      Tsubasa Hashimoto, Yuxin Ye, Asuka Matsuno, Yuki Ohnishi, Akira Kitamura, Masataka Kinjo, Satoshi Abe, Takafumi Uenod, Min Yao, Tomohisa Ogawa, Takashi Matsuia, Yoshikazu Tanaka
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 509 Issue: 2 Pages: 577-584

    • DOI

      10.1016/j.bbrc.2018.12.096

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SDS-induced oligomerization of Lys49-phospholipase A2 from snake venom2019

    • Author(s)
      Matsui Takashi、Kamata Shizuka、Ishii Kentaro、Maruno Takahiro、Ghanem Nouran、Uchiyama Susumu、Kato Koichi、Suzuki Atsuo、Oda-Ueda Naoko、Ogawa Tomohisa、Tanaka Yoshikazu
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2330-2330

    • DOI

      10.1038/s41598-019-38861-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cryo-EM reveals the asymmetric assembly of squid hemocyanin2019

    • Author(s)
      Tanaka, Y., Kato, S., Stabrin, M., Raunser, S., Matsui, T. & Gatsogiannis, C.
    • Journal Title

      International Union of Crystallography (IUCr)

      Volume: 6 Issue: 3 Pages: 426-437

    • DOI

      10.1107/s205225251900321x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] そのエピトープは創薬標的と成り得るか?:天然蛋白質の相互作用情報を利用したツール抗体設計2020

    • Author(s)
      勝木泰司, 中澤光, 松井崇, 田中良和, 梅津光央
    • Organizer
      第51回化学工学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 包括的な物性解析によって見えてきたハブ毒蛋白質のSDSによる多量体化2019

    • Author(s)
      松井崇, 鎌田しずか, 石井健太郎, 丸野孝浩, Ghanem Nouran, 内山進, 加藤 晃一, 鈴木淳巨, 上田直子, 小川智久, 田中良和
    • Organizer
      日本プロテオーム学会2019年大会 第70回日本電気泳動学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳の機能状態モニタリングを目指した脳脊髄液の詳細な比較分析への取り組み2019

    • Author(s)
      角田貴樹, 紺野亮, 板倉誠, 松井崇, 小寺義男
    • Organizer
      日本プロテオーム学会2019年大会 第70回日本電気泳動学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウスの小腸・大腸を対象としたペプチドーム解析の基礎的検討2019

    • Author(s)
      中川譲, 山田拓也, 佐藤雅, 松井崇, 板倉誠, 岩渕和也, 小寺義男
    • Organizer
      日本プロテオーム学会2019年大会 第70回日本電気泳動学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 安定同位体標識法とGeLC-MS/MS法を組み合わせたタンパク質存在様式の比較分析法の確立と応用2019

    • Author(s)
      伊藤大晃, 紺野亮, 福井朋也, 松井崇, 長塩亮, 佐藤雄一, 小寺義男
    • Organizer
      日本プロテオーム学会2019年大会 第70回日本電気泳動学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] スルメイカヘモシアニンの構造解析2019

    • Author(s)
      松井崇, 加藤早苗, 田中良和
    • Organizer
      日本結晶学会令和元年度年会および会員総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 水中拘束ストレスマウスの大脳皮質を対象とした包括的なタンパク質存在様式の比較分析2019

    • Author(s)
      紺野亮, 伊藤大晃, 樋口雅崇, 松井崇, 佐藤俊哉, 板倉誠, 小寺 義男
    • Organizer
      日本プロテオーム学会2019年大会 第70回日本電気泳動学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] S-SAD法を利用した海洋生物由来タンパク質の構造解析2019

    • Author(s)
      影山大夢,小野寺かこ,松井崇,小川智久,田中良和
    • Organizer
      2019年度量子ビームサイエンスフェスタ
    • Related Report
      2019 Research-status Report
  • [Presentation] ホスホリパーゼA2アナログの立体構造解析とSDSによる多量体化2019

    • Author(s)
      松井崇、鎌田しずか、石井健太郎、丸野孝浩、ガーネムノーラン、内山進、加藤晃一、鈴木淳臣、上田直子、小川智久、田中良和
    • Organizer
      2018年度量子ビームタイムサイエンスフェスタ
    • Related Report
      2018 Research-status Report
  • [Presentation] 蛋白質結晶中の巨大な空隙への蛋白質の包摂2019

    • Author(s)
      橋本翼、松井崇、小川智久、田中良和
    • Organizer
      2018年度量子ビームタイムサイエンスフェスタ
    • Related Report
      2018 Research-status Report
  • [Book] Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid Proteins2020

    • Author(s)
      Kato Sanae, Matsui Takashi, Tanaka Yoshikazu
    • Total Pages
      24
    • Publisher
      Springer
    • Related Report
      2019 Research-status Report
  • [Remarks] Matsui's Web Site

    • URL

      https://www.kitasato-u.ac.jp/sci/resea/buturi/seitai/matsui/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 新着情報

    • URL

      https://www.kitasato-u.ac.jp/sci/univ/physics/news/n20210301.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 新着情報

    • URL

      https://www.kitasato-u.ac.jp/sci/univ/physics/news/n20210308.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 北里大学理学部物理学科特設HP「宇宙から生命へ」

    • URL

      https://www.kitasato-u.ac.jp/sci/resea/buturi/phys_sp/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 北里大学理学部物理学科教員個人ページ

    • URL

      https://www.kitasato-u.ac.jp/sci/resea/buturi/seitai/matsui/

    • Related Report
      2019 Research-status Report
  • [Remarks] 東北大学生命科学研究科応用生命分子解析分野

    • URL

      https://www.lifesci.tohoku.ac.jp/labmos/

    • Related Report
      2019 Research-status Report
  • [Remarks] 北里大学若手lab

    • URL

      https://sites.google.com/view/wakatelab/main/past_events4?authuser=0

    • Related Report
      2019 Research-status Report
  • [Remarks] 北里大学理学部セミナー

    • URL

      https://www.kitasato-u.ac.jp/sci/research/seminar/sci_res_s_2019_10.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 応用生命分子解析分野 東北大学 - 東北大学 大学院 生命科学研究科

    • URL

      https://www.lifesci.tohoku.ac.jp/labmos/

    • Related Report
      2018 Research-status Report

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Published: 2018-01-25   Modified: 2022-01-27  

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