@article{ab7a581f850f4d40a314d59b5c02fd63,
title = "Structure snapshots reveal the mechanism of a bacterial membrane lipoprotein N-acyltransferase",
abstract = "Bacterial lipoproteins (BLPs) decorate the surface of membranes in the cell envelope. They function in membrane assembly and stability, as enzymes, and in transport. The final enzyme in the BLP synthesis pathway is the apolipoprotein N-acyltransferase, Lnt, which is proposed to act by a ping-pong mechanism. Here, we use x-ray crystallography and cryo-electron microscopy to chart the structural changes undergone during the progress of the enzyme through the reaction. We identify a single active site that has evolved to bind, individually and sequentially, substrates that satisfy structural and chemical criteria to position reactive parts next to the catalytic triad for reaction. This study validates the ping-pong mechanism, explains the molecular bases for Lnt's substrate promiscuity, and should facilitate the design of antibiotics with minimal off-target effects.",
author = "Luke Smithers and Oksana Degtjarik and Dietmar Weichert and Huang, {Chia Ying} and Coil{\'i}n Boland and Katherine Bowen and Abraham Oluwole and Corinne Lutomski and Robinson, {Carol V.} and Scanlan, {Eoin M.} and Meitian Wang and Vincent Olieric and Moran Shalev-Benami and Martin Caffrey",
note = "We thank past and present members of the MS&FB group for assorted contributions to this study. The assistance and support of beamline scientists at the Swiss Light Source (X06SA and X10SA) and the Diamond Light Source (I24) are acknowledged. We thank N. Elad for assisting with cryo-EM data collection and G. McManus for performing the fluorescence microscopy. Funding: The work was supported, in part, by Science Foundation Ireland grants 16/IA/4435 (to M.C.) and 19/FFP/6667 (to K.B. and E.M.S.); the European Union{\textquoteright}s Horizon 2020 research and innovation program under the European Research Council (ERC; grant no. 949364 to M.S.-B.); the Marie Sk{\l}odowska-Curie program (grant no. 701647 to C.-Y.H.); the Blavatnik Foundation (to M.C. and M.S.-B.); an Irish Research Council Postdoctoral Fellowship (GOIPD/2021/40 to L.S.); and the Zuckerman STEM Leadership Program (to M.S.-B.). D.W. was funded, in part, by Deutsche Forschungsgemeinschaft (German Research Foundation) WE 6084/1-1. Work in the C.V.R. laboratory was supported by Medical Research Council Project MR/V028839/1 and a Wellcome Trust Award (221795/Z/20/Z). M.S.-B. holds the Tauro Career Development Chair in Biomedical Research.",
year = "2023",
month = jun,
day = "30",
doi = "https://doi.org/10.1126/sciadv.adf5799",
language = "الإنجليزيّة",
volume = "9",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "26",
}