Mode of action of lipoprotein modification enzymes—Novel antibacterial targets,Molecular Microbiology

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Mode of action of lipoprotein modification enzymes—Novel antibacterial targets
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-09-26 , DOI: 10.1111/mmi.14610
Simon Legood _{1,

2,

3,

4} , Ivo G Boneca _{1,

2,

3} , Nienke Buddelmeijer _{1,

2,

3}

Affiliation

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.

中文翻译：

脂蛋白修饰酶的作用方式——新的抗菌靶点

脂蛋白的特点是其氨基末端有一个脂肪酸部分，通过该脂肪酸部分将脂蛋白锚定在膜上。它们在细菌细胞中履行多种基本功能，例如细胞壁维护、毒力、包括抗生素在内的有毒元素的流出以及营养物质的吸收。脂蛋白的翻译后修饰过程涉及完整膜酶和作为酰基供体的磷脂的连续作用。近年来，脂蛋白修饰酶的结构已通过 X 射线晶体学解析，从而可以更深入地了解其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，并且很容易被小分子接近。由于脂蛋白修饰途径在变形菌中至关重要，因此它是开发新型抗生素的潜在目标。在这篇综述中，我们讨论了有关酶结构表征的最新文献，以及与抑制剂高通量筛选相兼容的体外活性测定，并展望了新型抗菌药物的开发。

更新日期：2020-09-26

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