The first small-molecule inhibitors of members of the ribonuclease E family.
The first small-molecule inhibitors of members of the ribonuclease E family.
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DOI：
10.1038/srep08028
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发表时间：
2015-01-26
影响因子：
4.6
通讯作者：
McDowall KJ
中科院分区：
文献类型：
--
作者：
Kime L;Vincent HA;Gendoo DM;Jourdan SS;Fishwick CW;Callaghan AJ;McDowall KJ
大肠杆菌核糖核酸内切酶RNase E是所有类型RNA加工和降解的核心，因此是基因表达的多效性调节剂。它对生长至关重要，是能够识别RNA的5 ' -单磷酸化末端从而提高许多切割效率的内切酶的第一个例子之一。RNase E的同源物可以在许多细菌家族中发现，包括重要的病原体，但在人类或动物中尚未发现同源物。RNase E代表了开发新抗生素的潜在目标，以对抗目前使用的抗生素中越来越多的耐药细菌。结合必需酶活性位点的强效小分子抑制剂被证明是潜在药物线索的来源，也是通过化学遗传学解剖功能的工具。在这里，我们报告了使用虚拟高通量筛选来获得预测在RNase E的n端催化一半位点结合的小分子。我们表明，这些化合物能够特异性结合并抑制大肠杆菌和结核分枝杆菌的RNase E的催化作用，并且还抑制RNase E的一种类似物RNase G的活性。
The Escherichia coli endoribonuclease RNase E is central to the processing and degradation of all types of RNA and as such is a pleotropic regulator of gene expression. It is essential for growth and was one of the first examples of an endonuclease that can recognise the 5′-monophosphorylated ends of RNA thereby increasing the efficiency of many cleavages. Homologues of RNase E can be found in many bacterial families including important pathogens, but no homologues have been identified in humans or animals. RNase E represents a potential target for the development of new antibiotics to combat the growing number of bacteria that are resistant to antibiotics in use currently. Potent small molecule inhibitors that bind the active site of essential enzymes are proving to be a source of potential drug leads and tools to dissect function through chemical genetics. Here we report the use of virtual high-throughput screening to obtain small molecules predicted to bind at sites in the N-terminal catalytic half of RNase E. We show that these compounds are able to bind with specificity and inhibit catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also inhibit the activity of RNase G, a paralogue of RNase E.
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影响因子：
11
作者：
Kaberdin VR;Singh D;Lin-Chao S
通讯作者：
Lin-Chao S
影响因子：
64.8
作者：
Mackie, GA
通讯作者：
Mackie, GA
影响因子：
2.9
作者：
Callaghan, AJ;Grossmann, JG;Luisi, BF
通讯作者：
Luisi, BF
影响因子：
3.6
作者：
Lee, K;Bernstein, JA;Cohen, SN
通讯作者：
Cohen, SN
DOI：
10.1073/pnas.0401382101
发表时间：
2004-06-22
影响因子：
11.1
作者：
Jiang, XQ;Belasco, JG
通讯作者：
Belasco, JG