Article Metrics


Online attention

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

DOI: 10.1038/ncomms15952 DOI Help

Authors: Maciej Wiktor (Trinity College, Dublin) , Dietmar Weichert (Trinity College, Dublin) , Nicole Howe (Trinity College Dublin) , Chia-Ying Huang (Trinity College Dublin; Swiss Light Source) , Vincent Olieric (Swiss Light Source) , CoilĂ­n Boland (Trinity College Dublin) , Jonathan Bailey (Trinity College Dublin) , Lutz Vogeley (Trinity College Dublin) , Phillip J. Stansfeld (University of Oxford) , Nienke Buddelmeijer (Institut Pasteur) , Meitian Wang (Trinity College Dublin) , Martin Caffrey (Trinity College Dublin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 8

State: Published (Approved)
Published: July 2017
Diamond Proposal Number(s): 11890 , 12710

Open Access Open Access

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.

Journal Keywords: Enzyme mechanisms

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: X06SA, X10SA at SLS; 23-ID at APS

Added On: 09/11/2017 13:41


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)