18-Crown-6-ether使用明显的体相互作用来解多药物输出 EmrE
Merissa Brousseau1, Tapasyatanu Dash2, Michael J Rourke3
1Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
从大肠杆菌的多药物排泄EmrE可以作为治疗点. 我们发现18-皇冠-6-以太结合于lysine 22, 诱导质子泄漏,
科学领域:
- 生物化学
- 分子生物学
- 微生物学
背景情况:
- 大肠杆菌的多种药物排放EmrE具有多种传输功能,具有潜在的治疗标.
- 小分子基质可以诱导运输体依赖的敏感性,与典型的抗生素耐药性表型形成鲜明对比.
研究的目的:
- 研究小分子基质18-crown-6-ether在EmrE转运器上的结合部位和作用机制.
- 阐明 lysine 22 和 threonine 56 在 EmrE 传输的全质调节中的作用.
主要方法:
- 用核磁共振 (NMR) 的化学转移扰动来确定18-crown-6-ether的结合部位.
- 使用体内EC50测定和脂质体泄漏测定来评估输送物的活性和基质诱导的影响.
主要成果:
- 证实18- 皇冠-6- 以太与EmrE载体的lysine 22 (K22) 结合.
- 这种基质被证明会触发不合的质子泄漏,表明正常的传输调节被破坏.
- 对K22的突变分析进一步巩固了该残留物和T56在全调节中的重要性.
结论:
- 氨酸22是对EmrE全调节的关键残留物,特别是在与C端尾相互作用时.
- 了解EmrE的传输机制和受敏基质的调节,可以为其他多药性排泄提供见解.
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