...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of bacteriology >Mutational Analysis of the Multiple-Antibiotic Resistance Regulator MarR Reveals a Ligand Binding Pocket at the Interface between the Dimerization and DNA Binding Domains
【24h】

Mutational Analysis of the Multiple-Antibiotic Resistance Regulator MarR Reveals a Ligand Binding Pocket at the Interface between the Dimerization and DNA Binding Domains

机译：多种抗生素抗性调节剂MarR的突变分析揭示了二聚化和DNA结合域之间界面上的配体结合口袋。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Escherichia coli regulator MarR represses the multiple-antibiotic resistance operon marRAB and responds to phenolic compounds, including sodium salicylate, which inhibit its activity. Crystals obtained in the presence of a high concentration of salicylate indicated two possible salicylate sites, SAL-A and SAL-B. However, it was unclear whether these sites were physiologically significant or were simply a result of the crystallization conditions. A study carried out on MarR homologue MTH313 suggested the presence of a salicylate binding site buried at the interface between the dimerization and the DNA-binding domains. Interestingly, the authors of the study indicated a similar pocket conserved in the MarR structure. Since no mutagenesis analysis had been performed to test which amino acids were essential in salicylate binding, we examined the role of residues that could potentially interact with salicylate. We demonstrated that mutations in residues shown as interacting with salicylate at SAL-A and SAL-B in the MarR-salicylate structure had no effect on salicylate binding, indicating that these sites were not the physiological regulatory sites. However, some of these residues (P57, R86, M74, and R77) were important for DNA binding. Furthermore, mutations in residues R16, D26, and K44 significantly reduced binding to both salicylate and 2,4-dinitrophenol, while a mutation in residue H19 impaired the binding to 2,4-dinitrophenol only. These findings indicate, as for MTH313, the presence of a ligand binding pocket located between the dimerization and DNA binding domains.
机译：大肠杆菌调节剂MarR抑制多重抗生素抗性操纵子 marRAB 并响应酚类化合物（包括水杨酸钠），从而抑制其活性。在高浓度水杨酸盐存在下获得的晶体表明两个可能的水杨酸盐位点，SAL-A和SAL-B。但是，尚不清楚这些位点在生理上是重要的还是仅仅是结晶条件的结果。对MarR同源物MTH313进行的研究表明，在二聚化和DNA结合结构域之间的界面处埋藏着水杨酸酯结合位点。有趣的是，研究的作者指出了MarR结构中保守的类似口袋。由于尚未进行诱变分析来测试哪些氨基酸在水杨酸酯结合中必不可少，因此我们研究了可能与水杨酸酯相互作用的残基的作用。我们证明了在MarR-水杨酸盐结构中显示为与水杨酸盐在SAL-A和SAL-B相互作用的残基中的突变对水杨酸盐结合没有影响，表明这些位点不是生理调控位点。但是，其中一些残基（P57，R86，M74和R77）对于DNA结合很重要。此外，残基R16，D26和K44中的突变显着降低了与水杨酸酯和2,4-二硝基苯酚的结合，而残基H19中的突变仅削弱了与2,4-二硝基苯酚的结合。这些发现表明，对于MTH313，位于二聚化和DNA结合结构域之间的配体结合袋的存在。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号