Project/Area Number |
24780088
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Applied microbiology
|
Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
MORI Shigetarou 国立感染症研究所, 細菌第二部, 室長 (60425676)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
|
Keywords | 結核菌 / X線結晶構造解析 / 非結核性抗酸菌 / 加リン酸分解酵素 / ドラッグデザイン / 新規抗結核薬 / ヌクレオチド / 抗酸菌 / 加リン酸分解 / インシリコスクリーニング |
Outline of Final Research Achievements |
It was revealed that the flexibility of a loop, which is located in the active site of diadenosine tetraphosphate phosphorylase from Mycobacterium tuberculosis (MtAPA), might be correlated with substrate specificity of MtAPA. Based on the results of the structure-function analysis of MtAPA, new inhibitors of MtAPA were found. Moreover, it was showed that the MtAPA homologous proteins from M. avium and M. smegmatis possess diadenosine tetraphosphate phosphorylase activities and that the new inhibitors of MtAPA could inhibit the activities of these proteins. On the other hand, it was revealed that Rv2614c protein from M. tuberculosis is an aminoacyl-tRNA synthetase. It was expected that the results in this study would be valuable in elucidating the mechanism of intracellular parasitism of M. tuberculosis and developing the new anti-tuberculosis drugs.
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