Abstract
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.
Highlights
Volkmar Braun first discovered bacterial lipoproteins in 1973 through the identification of a fatty-acid modification of Lpp, or Braun's lipoprotein, in E. coli (Hantke and Braun, 1973)
This study demonstrated the incorporation of palmitic acid from phospholipid through an amide bond in S-diacylglycerylcysteine
Pyridine imidazole compounds were shown to interfere with LolE and LolC (McLeod et al, 2015), and a pyrazole compound inhibits the LolCDE complex (Nayar et al, 2015). These results demonstrate the importance of outer membrane (OM) lipoproteins in cell wall biogenesis and viability
Summary
Volkmar Braun first discovered bacterial lipoproteins in 1973 through the identification of a fatty-acid modification of Lpp, or Braun's lipoprotein, in E. coli (Hantke and Braun, 1973). New and exciting insights have been obtained in recent years on the molecular mechanism of lipoprotein modification enzymes and their structural arrangements in the membrane.
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