Structural biochemistry of translation-related proteins from pathogenic bacteria
| Project/Area Number |
16K05859
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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 |
Bio-related chemistry
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| Research Institution | Juntendo University (2019)
Institute of Physical and Chemical Research (2016-2018) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 翻訳 / バイオテクノロジー / タンパク質 / アミノアシルtRNA合成酵素 / tRNA / ケミカルバイオロジー / 病原性細菌 / 抗生物質 / 翻訳後修飾 / 非天然型アミノ酸 / X線結晶構造解析 / クロスリンカー / 細菌 / 酵素 / 蛋白質 |
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| Outline of Final Research Achievements |
The translation factor EF-P is a bacterial L-shaped protein that alleviates the ribosome stalling that occurs at consequtive prolines in the genetic code translation. In N. meningitidis EF-P, rhamnosylation of the arginine residue at the L-shaped tip is very important for its activity. We solved the crystal structure of the rhamnosylation enzyme EarP and the EarP / EF-P complex from N. meningitidis, and identified amino acid residues important for Arg32 rhamnosylation activity. The conformation of the rhamnose moiety is suitable for the reaction was estimated by the docking simulation, and the reaction mechanism of EF-P(Arg32) rhamnosylation was proposed.
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| Academic Significance and Societal Importance of the Research Achievements |
EF-PやEF-Pの翻訳後修飾は細菌にだけ存在し、一方ヒトなどの真核生物では全く修飾が異なるeIF-5AがEF-Pの役割を担っている。ラムノシル化修飾酵素EarPは髄膜炎菌、淋菌緑膿菌、百日咳菌、セパシア菌などの臨床的に重要な病原菌にのみ存在する。従って細菌にしか存在しないEF-P修飾酵素を阻害する化合物を設計すれば感染症を引き起こす病原菌や薬剤耐性菌に対して副作用の無い有効な抗菌薬にすることが期待できる。このような阻害剤を開発することで、ヒトやその体内に存在する腸内細菌、常在細菌に悪影響を及ぼさず、特定の病原細菌のみを退治できる有効な抗菌剤の開発に繋がると期待される。
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Report
(5 results)
Research Products
(31 results)
