2020 Fiscal Year Final Research Report
Identification of novel antibacterial compound produced by artificial prenyltransferase.
Project/Area Number |
17KK0141
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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Allocation Type | Multi-year Fund |
Research Field |
Structural biochemistry
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Research Institution | Kitasato University (2019-2020) Tohoku University (2017-2018) |
Principal Investigator |
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Project Period (FY) |
2018 – 2020
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Keywords | FtsZ / プレニル基転移酵素 / 電子顕微鏡 / LC-MS |
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.
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Free Research Field |
構造生物学
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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。
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