8AQ4

In surfo structure of the membrane integral lipoprotein N-acyltransferase Lnt from E. coli in complex with TITC and lyso-PE

Summary for 8AQ4

• Entry DOI: 10.2210/pdb8aq4/pdb
• Descriptor: Apolipoprotein N-acyltransferase, CHLORIDE ION, 1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE, ... (11 entities in total)
• Functional Keywords: lnt, apolipoprotein n-acyltransferase, bacterial lipoproteins., transferase
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 1
• Total formula weight: 64993.94

Authors

Huang, C.-Y.,Weichert, D.,Boland, C.,Smithers, L.,Olieric, V.,Wang, M.,Caffrey, M. (deposition date: 2022-08-11, release date: 2023-07-12, Last modification date: 2024-10-23)

Primary citation

Smithers, L.,Degtjarik, O.,Weichert, D.,Huang, C.Y.,Boland, C.,Bowen, K.,Oluwole, A.,Lutomski, C.,Robinson, C.V.,Scanlan, E.M.,Wang, M.,Olieric, V.,Shalev-Benami, M.,Caffrey, M.
Structure snapshots reveal the mechanism of a bacterial membrane lipoprotein N -acyltransferase.
Sci Adv, 9:eadf5799-eadf5799, 2023

PubMed 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 -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.

PubMed: 37390210
DOI: 10.1126/sciadv.adf5799

Experimental method

X-RAY DIFFRACTION (2.62 Å)