Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis.

Abstract : Lipoproteins serve essential roles in the bacterial cell envelope. The posttranslational modification pathway leading to lipoprotein synthesis involves three enzymes. All are potential targets for the development of new antibiotics. Here we report the crystal structure of the last enzyme in the pathway, apolipoprotein N-acyltransferase, Lnt, responsible for adding a third acyl chain to the lipoprotein's invariant diacylated N-terminal cysteine. Structures of Lnt from Pseudomonas aeruginosa and Escherichia coli have been solved; they are remarkably similar. Both consist of a membrane domain on which sits a globular periplasmic domain. The active site resides above the membrane interface where the domains meet facing into the periplasm. The structures are consistent with the proposed ping-pong reaction mechanism and suggest plausible routes by which substrates and products enter and leave the active site. While Lnt may present challenges for antibiotic development, the structures described should facilitate design of therapeutics with reduced off-target effects.
Keywords : Enzyme mechanisms
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Article dans une revue
Nature Communications, Nature Publishing Group, 2017, 8, pp.15952. 〈10.1038/ncomms15952〉
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Maciej Wiktor, Dietmar Weichert, Nicole Howe, Chia-Ying Huang, Vincent Olieric, et al.. Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis.. Nature Communications, Nature Publishing Group, 2017, 8, pp.15952. 〈10.1038/ncomms15952〉. 〈pasteur-01561000〉

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