通过局部重新折叠RNA聚合酶结构的转录失活
Georgiy A Belogurov1, Marina N Vassylyeva, Anastasiya Sevostyanova
1Department of Microbiology, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA.
Nature
|October 24, 2008
概括
米克索皮罗宁抗生素通过阻断转录启动复合体的形成来抑制细菌RNA聚合酶 (RNAP). 结构研究表明,dMyx结合稳定了RNAP切换-2,阻碍了DNA化的传播.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 抗生素结构研究有助于药物设计,揭示了分子机制.
- 米克索皮罗宁抗生素通过一种未被描述的机制抑制细菌RNA聚合酶 (RNAP).
研究的目的:
- 阐明myxopyronin抑制细菌RNAP的结构基础.
- 描述dMyx和Thermus thermophilus RNAP全酶之间的相互作用.
主要方法:
- 用X射线晶体学来确定dMyx的复杂结构,使用Thermus thermophilus RNAP全酶.
- 用DNA足迹测试来评估dMyx对DNA融化的影响.
主要成果:
- 抗生素dMyx与RNAP头域中的一个口袋结合,靠近DNA模板链.
- dMyx结合稳定了β'-子单元切换-2段,阻止了DNA融向活性部位的传播.
- 交换机-2中的突变模仿了dMyx效应,表明其作为监管检查点的作用.
结论:
- 米克索皮罗宁是一种新的抗生素类别,其向的是前催化转录启动复合体.
- 该研究提出了dMyx作用的机制,并强调了RNAP开关-2在DNA加载和调节中的作用.
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