Institut Pasteur, Unité Biologie et Génétique de la Paroi Bactérienne, Paris, France.
CNRS, UMR 2001 « Microbiologie intégrative et Moléculaire », Paris, France.
Mol Microbiol. 2021 Mar;115(3):356-365. doi: 10.1111/mmi.14610. Epub 2020 Oct 12.
Lipoproteins are characterized by a fatty acid moiety at their amino-terminus through which they are anchored into membranes. They fulfill a variety of essential functions in bacterial cells, such as cell wall maintenance, virulence, efflux of toxic elements including antibiotics, and uptake of nutrients. The posttranslational modification process of lipoproteins involves the sequential action of integral membrane enzymes and phospholipids as acyl donors. In recent years, the structures of the lipoprotein modification enzymes have been solved by X-ray crystallography leading to a greater insight into their function and the molecular mechanism of the reactions. The catalytic domains of the enzymes are exposed to the periplasm or external milieu and are readily accessible to small molecules. Since the lipoprotein modification pathway is essential in proteobacteria, it is a potential target for the development of novel antibiotics. In this review, we discuss recent literature on the structural characterization of the enzymes, and the in vitro activity assays compatible with high-throughput screening for inhibitors, with perspectives on the development of new antimicrobial agents.
脂蛋白的特点是其氨基末端有一个脂肪酸部分，通过该部分将其锚定在膜上。它们在细菌细胞中发挥着多种重要功能，如细胞壁的维持、毒力、包括抗生素在内的有毒元素的外排以及营养物质的摄取。脂蛋白的翻译后修饰过程涉及整合膜酶和磷脂作为酰基供体的顺序作用。近年来，通过 X 射线晶体学解决了脂蛋白修饰酶的结构问题，从而更深入地了解了它们的功能和反应的分子机制。酶的催化结构域暴露于周质或外部环境中，很容易被小分子接触。由于脂蛋白修饰途径在变形菌中是必不可少的，因此它是开发新型抗生素的潜在目标。在这篇综述中，我们讨论了关于酶的结构特征的最新文献，以及与抑制剂高通量筛选兼容的体外活性测定，以期开发新的抗菌药物。
