M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Sci Rep. 2013;3:1678. doi: 10.1038/srep01678.
Bacterial cell wall is targeted by many antibiotics. Among them are lantibiotics, which realize their function via interaction with plasma membrane lipid-II molecule - a chemically conserved part of the cell wall synthesis pathway. To investigate structural and dynamic properties of this molecule, we have performed a series of nearly microsecond-long molecular dynamics simulations of lipid-II and some of its analogs in zwitterionic single component and charged mixed simulated phospholipid bilayers (the reference and the mimic of the bacterial plasma membrane, respectively). Extensive analysis revealed that lipid-II forms a unique "amphiphilic pattern" exclusively on the surface of the simulated bacterial membrane (and not in the reference one). We hypothesize that many lantibiotics exploit the conserved features of lipid-II along with characteristic modulation of the bacterial membrane as the "landing site". This putative recognition mechanism opens new opportunities for studies on lantibiotics action and design of novel armament against resistant bacterial strains.
细菌细胞壁是许多抗生素的作用靶点。其中包括类脂肽抗生素，它们通过与细胞膜脂质 II 分子相互作用来实现其功能 - 脂质 II 分子是细胞壁合成途径中化学保守的一部分。为了研究该分子的结构和动态特性，我们对脂质 II 及其一些类似物在两性离子单组分和带电混合模拟磷脂双层中的近微秒长的分子动力学模拟进行了一系列研究（分别是细菌细胞膜的参考和模拟物）。广泛的分析表明，脂质 II 仅在模拟细菌膜的表面形成独特的“两亲性模式”（而不是在参考物中）。我们假设许多类脂肽抗生素利用脂质 II 的保守特征以及细菌膜的特征调制作为“着陆点”。这种假设的识别机制为研究类脂肽抗生素的作用和设计针对耐药菌株的新型武器开辟了新的机会。
