PDF(Pubmed)
Abstract：
Bacteria are known to be constantly adapting to become resistant to antibiotics. Currently, efficient antibacterial compounds are still available; however, it is only a matter of time until these compounds also become inefficient. Ribonucleases are the enzymes responsible for the maturation and degradation of RNA molecules, and many of them are essential for microbial survival. Members of the PNPase and RNase II families of exoribonucleases have been implicated in virulence in many pathogens and, as such, are valid targets for the development of new antibacterials. In this paper, we describe the use of virtual high-throughput screening (vHTS) to identify chemical compounds predicted to bind to the active sites within the known structures of RNase II and PNPase from Escherichia coli. The subsequent in vitro screening identified compounds that inhibited the activity of these exoribonucleases, with some also affecting cell viability, thereby providing proof of principle for utilizing the known structures of these enzymes in the pursuit of new antibacterials.
摘要：
已知细菌不断适应变得对抗生素具有抗性。目前,有效的抗菌化合物仍然可用；然而，这些化合物也变得低效只是时间问题。核糖核酸酶是负责RNA分子成熟和降解的酶，其中许多是微生物生存所必需的。PNPase和RNaseII家族的成员在许多病原体中都与毒力有关，因此，是开发新抗菌药物的有效目标。在本文中,我们描述了使用虚拟高通量筛选（vHTS）来鉴定预测与大肠杆菌RNaseII和PNPase已知结构内的活性位点结合的化合物。随后的体外筛选鉴定了抑制这些外切核糖核酸酶活性的化合物，有些也会影响细胞的活力，从而为利用这些酶的已知结构寻找新的抗菌药物提供了原理证据。
