TY - JOUR
T1 - Structure snapshots reveal the mechanism of a bacterial membrane lipoprotein N-acyltransferase
AU - Smithers, Luke
AU - Degtjarik, Oksana
AU - Weichart, Dietmar
AU - Huang, Chia-Ying
AU - Boland, Coilín
AU - Bowan, Katherine
AU - Oluwole, Abraham
AU - Lutomski, Corinne
AU - Robinson, Carol
AU - Scanlan, Eoin
AU - Wang, Meitian
AU - Olieric, Vincent
AU - Shalev-Benami, Moran
AU - Caffrey, Martin
PY - 2023/6/30
Y1 - 2023/6/30
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.adf5799
DO - 10.1126/sciadv.adf5799
M3 - Article
C2 - 37390210
SN - 2375-2548
VL - 9
SP - eadf5799
JO - Science Advances
JF - Science Advances
IS - 26
M1 - eadf5799
ER -