期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 7, 页码 5149-5156出版社
ELSEVIER
DOI: 10.1074/jbc.M112.419069
关键词
-
资金
- Early Stage Research Training Scholarship (EU)
- Biotechnology and Biological Sciences Research Council (UK) [BB/J004561/1]
- John Innes Foundation
- National Research Foundation of South Africa
- Biotechnology and Biological Sciences Research Council [BBS/E/J/00000201] Funding Source: researchfish
Tuberculosis and other bacterial diseases represent a significant threat to human health. The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents. Naphthoquinones (e.g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis. We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases. Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction. We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site. This novel mode of action could be exploited to develop new antibacterial agents.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据