Structure snapshots reveal the mechanism of a bacterial membrane lipoprotein N-acyltransferase

Luke Smithers, Oksana Degtjarik, Dietmar Weichart, Chia-Ying Huang, Coilín Boland, Katherine Bowan, Abraham Oluwole, Corinne Lutomski, Carol Robinson, Eoin Scanlan, Meitian Wang, Vincent Olieric, Moran Shalev-Benami, Martin Caffrey

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.
Original languageEnglish
Article numbereadf5799
Pages (from-to)eadf5799
Number of pages17
JournalScience Advances
Issue number26
Publication statusPublished - 30 Jun 2023
Externally publishedYes


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