Origination of antibiotic drugs for tuberculosis based on the structural analyses of novel target proteins
Project/Area Number |
15K07909
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Physical pharmacy
|
Research Institution | Mukogawa Women's University |
Principal Investigator |
YAMASHITA Taku 武庫川女子大学, 薬学部, 准教授 (70398246)
|
Co-Investigator(Kenkyū-buntansha) |
宇野 公之 大阪大学, 薬学研究科, 教授 (00183020)
辻野 博文 大阪大学, 薬学研究科, 助教 (10707144)
|
Co-Investigator(Renkei-kenkyūsha) |
TAKESHITA Kohei 大阪大学, たんぱく質研究所, 招へい教員 (80346808)
ARAI Masayoshi 大阪大学, 薬学部, 特任教授 (80311231)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 結核菌 / 抗結核薬 / 構造解析 / ドッキングシミュレーション / 創薬 / 作用機序解明 / 結晶構造解析 |
Outline of Final Research Achievements |
BCG3185c is a novel protein from M. Tuberculosis, and the protein is emerged to be a target of Agelasine D. Agelasine D is derived from Marine sponge and shows inhibition to a tubercle bacillus. In order to clarify mechanism of the inhibition, we performed purification and X-ray crystallographic analysis on BCG3185c protein. Although co-crystallization of BCG3185c and Agelasine D was extremely difficult, we succeeded to acquire structural information on BCG3185c protein without Agelasine D. Subsequently, we performed docking simulation on Agelasine D to BCG3185c, and the results suggested that several aromatic amino acids in BCG3185c could be critical for binding of Agelasine D. While, we have been exploring other target protein for Helicyclamine A, an antibiotic for tuberculosis, and BCG2664 was identified to be a candidate applied for tuberculosis. Finally, we could establish a protocol for purification of BCG2664 protein.
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Report
(4 results)
Research Products
(1 results)