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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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
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Keywords | FtsZ / 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.
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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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Report
(4 results)
Research Products
(30 results)
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[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
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 15259-15259
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 509
Issue: 2
Pages: 577-584
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
International Union of Crystallography (IUCr)
Volume: 6
Issue: 3
Pages: 426-437
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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