Bacterial Cell Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Bioorg Chem. 2014 Aug;55:27-38. doi: 10.1016/j.bioorg.2014.03.007. Epub 2014 Apr 4.
Proteins involved in bacterial cell division often do not have a counterpart in eukaryotic cells and they are essential for the survival of the bacteria. The genetic accessibility of many bacterial species in combination with the Green Fluorescence Protein revolution to study localization of proteins and the availability of crystal structures has increased our knowledge on bacterial cell division considerably in this century. Consequently, bacterial cell division proteins are more and more recognized as potential new antibiotic targets. An international effort to find small molecules that inhibit the cell division initiating protein FtsZ has yielded many compounds of which some are promising as leads for preclinical use. The essential transglycosylase activity of peptidoglycan synthases has recently become accessible to inhibitor screening. Enzymatic assays for and structural information on essential integral membrane proteins such as MraY and FtsW involved in lipid II (the peptidoglycan building block precursor) biosynthesis have put these proteins on the list of potential new targets. This review summarises and discusses the results and approaches to the development of lead compounds that inhibit bacterial cell division.
参与细菌细胞分裂的蛋白质通常在真核细胞中没有对应物,它们对细菌的生存是必不可少的。许多细菌物种的遗传可及性,结合绿色荧光蛋白(GFP)的革命,用于研究蛋白质的定位以及晶体结构的可用性,在本世纪大大增加了我们对细菌细胞分裂的认识。因此,细菌细胞分裂蛋白越来越被认为是潜在的新抗生素靶标。一项旨在寻找抑制起始蛋白 FtsZ 的小分子的国际努力已经产生了许多化合物,其中一些具有作为临床前用途的先导化合物的潜力。肽聚糖合成酶的必需转糖基酶活性最近已可用于抑制剂筛选。用于关键的膜整合蛋白(如涉及脂质 II 生物合成的 MraY 和 FtsW)的酶促测定和结构信息已将这些蛋白列入潜在新靶标的名单。这篇综述总结和讨论了抑制细菌细胞分裂的先导化合物的发展结果和方法。