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Mode of action of lipoprotein modification enzymes—Novel antibacterial targets

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.
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Submitted on : Tuesday, May 18, 2021 - 8:46:21 AM
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Legood 2021 MolMic.pdf
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Simon Legood, Ivo G. Boneca, Nienke Buddelmeijer. Mode of action of lipoprotein modification enzymes—Novel antibacterial targets. Molecular Microbiology, Wiley, 2020, 115 (3), pp.356 - 365. ⟨10.1111/mmi.14610⟩. ⟨pasteur-03228295⟩



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