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Drug design based on a novel crystal structure of cytochrome bd oxidase in the respiratory chain.

Research Project

Project/Area Number 16K07299
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionKyushu Institute of Technology

Principal Investigator

Sakamoto Junshi  九州工業大学, 大学院情報工学研究院, 教授 (80175364)

Research Collaborator Michel Hartmut  
Safarian Schara  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords呼吸鎖 / シトクロム / 好熱性細菌 / アミノ酸生産菌 / グラム陽性菌 / 生体エネルギー変換 / 電子伝達系 / コリネバクテリウム / シトクロムbd / キノールオキシダーゼ
Outline of Final Research Achievements

Many organisms obtain energy from respiration. The molecular apparatuses to oxidize (mildly burn) organic compound in food with absorbed oxygen are called respiratory oxidases. There are two main types of oxidases. One is the heme-copper oxidase, which operates in human and animal bodies, and whose precise structure was solved in 1995 and has been investigated extensively. The other is cytochrome oxidase, which works in most prokaryotes including many pathogens, but not in eukaryotes. Within the period of this study, we published the first atomic structure of cytochrome oxidase in the world, under collaboration with a group in Germany. Since the revealed stereo-structure is totally different from that of heme-copper oxidase, it is a promising basis to design a new type of anti-bacterial drugs to overcome infectious diseases without adverse effects to humans and animals.

Academic Significance and Societal Importance of the Research Achievements

本研究で精密な分子構造の解明に成功したシトクロムbd型酸化酵素は、従来から解明されていたヘム銅型酸化酵素とは異なり、ヒトや家畜には存在せず、結核菌やジフテリア菌、MRSAを含む黄色ブドウ球菌など多くの病原菌の生存や毒性に関与している。これらの病原菌では、従来の医薬品が効かない耐性菌の発生が、先進国と発展途上国の両方で大きな問題となっている。今回の精密構造に基づき、新しい阻害剤を設計したり探索したりすることにより、これまでより作用が強かったり耐性を回避できる新タイプの抗感染症薬を創出できる道が開かれた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Int'l Joint Research] Max Planck Institute of Biophysics(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] マックスプランク生物物理学研究所(ドイツ)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Structure of a bd oxidase indicates similar mechanisms for membrane-integrated oxygen reductases.2016

    • Author(s)
      Safarian S, Rajendran C, Muller H, Preu J, Langer JD, Ovchinnikov S, Hirose T, Kusumoto T, Sakamoto J, Michel H.
    • Journal Title

      Science

      Volume: 352 Issue: 6285 Pages: 583-586

    • DOI

      10.1126/science.aaf2477

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] アミノ酸産生菌における呼吸鎖化還元酵素の拡張型超複合体構造解析2018

    • Author(s)
      平川可純, 石橋 航, 楠本朋一郎, 坂本順司, 安永卓生
    • Organizer
      第60 回 日本顕微鏡学会九州支部集会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 呼吸鎖シトクロムbdオキシダーゼの多様性:グラム陽性菌内部でさえ大きい2017

    • Author(s)
      中垣沙也香、広瀬太一朗、吉田 宰、坂本順司
    • Organizer
      日本生体エネルギー研究会第43回討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cytochrome bd-type quinol oxidases: structural variety even within the Gram-positive bacteria.2016

    • Author(s)
      Junshi Sakamoto, Tsukasa Yoshida, Taichiro Hirose, Tomoichirou Kusumoto.
    • Organizer
      19th Eropean Bioenergetics Conference
    • Place of Presentation
      Riva del Garda, Italy
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Cytochrome bd Oxidases Possess a Unique Protein Structure and an Unexpected Heme Group Arrangement.2016

    • Author(s)
      Schara Safarian, Chitra Rajendran, Hannelore Muller, Julia Preu, Julian D. Langer, Sergey Ovchinnikov, Taichiro Hirose, Tomoichirou, Kusumoto, Junshi Sakamoto, Hartmut Michel
    • Organizer
      19th Eropean Bioenergetics Conference
    • Place of Presentation
      Riva del Garda, Italy
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The first atomic structure of cytohrome bd-type respiratory oxidase2016

    • Author(s)
      Junshi Sakamoto
    • Organizer
      The 4th International ALA and Porphyrin Symposium
    • Place of Presentation
      Ryojun Hall of Nagasaki University
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 基礎分子遺伝学・ゲノム科学2018

    • Author(s)
      坂本順司
    • Total Pages
      238
    • Publisher
      裳華房
    • ISBN
      9784785352370
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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