期刊
NUCLEIC ACIDS RESEARCH
卷 39, 期 9, 页码 3917-3927出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq1296
关键词
-
资金
- British Society for Antimicrobial Chemotherapy [GA741]
- UK Overseas Research Students Awards Scheme
- University of Bristol
- Human Frontiers Science Program [RGP0031/2007]
- Research Corporation for Science Advancement, Cottrell College [10493]
- UK Biotechnology and Biological Sciences Research Council [719/B15474, 719/REI20571]
- UK Northwest Structural Genomics Centre (NWSGC) [MAD10]
- North West Development Agency [N0002170]
Quinolones inhibit bacterial type II DNA topoisomerases (e.g. DNA gyrase) and are among the most important antibiotics in current use. However, their efficacy is now being threatened by various plasmid-mediated resistance determinants. Of these, the pentapeptide repeat-containing (PRP) Qnr proteins are believed to act as DNA mimics and are particularly prevalent in Gram-negative bacteria. Predicted Qnr-like proteins are also present in numerous environmental bacteria. Here, we demonstrate that one such, Aeromonas hydrophila AhQnr, is soluble, stable, and relieves quinolone inhibition of Escherichia coli DNA gyrase, thus providing an appropriate model system for Gram-negative Qnr proteins. The AhQnr crystal structure, the first for any Gram-negative Qnr, reveals two prominent loops (1 and 2) that project from the PRP structure. Deletion mutagenesis demonstrates that both contribute to protection of E. coli DNA gyrase from quinolones. Sequence comparisons indicate that these are likely to be present across the full range of Gram-negative Qnr proteins. On this basis we present a model for the AhQnr:DNA gyrase interaction where loop1 interacts with the gyrase A 'tower' and loop2 with the gyrase B TOPRIM domains. We propose this to be a general mechanism directing the interactions of Qnr proteins with DNA gyrase in Gram-negative bacteria.
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