Drug design based on a novel crystal structure of cytochrome bd oxidase in the respiratory chain.
| Project/Area Number |
16K07299
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kyushu Institute of Technology |
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Principal Investigator |
Sakamoto Junshi 九州工業大学, 大学院情報工学研究院, 教授 (80175364)
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| Research Collaborator |
Michel Hartmut
Safarian Schara
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(9 results)
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[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
Int'l Joint Research
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