5N6L

Structure of the membrane integral lipoprotein N-acyltransferase Lnt C387A mutant from E. coli

Summary for 5N6L

• Entry DOI: 10.2210/pdb5n6l/pdb
• Descriptor: Apolipoprotein N-acyltransferase, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, GLYCEROL, ... (4 entities in total)
• Functional Keywords: membrane protein, lipoprotein, n-acyltransferase, lipidic cubic phase, transferase
• Biological source: Escherichia coli (strain K12)
• Total number of polymer chains: 2
• Total formula weight: 129229.10

Authors

Huang, C.-Y.,Boland, C.,Howe, N.,Wiktor, M.,Vogeley, L.,Weichert, D.,Bailey, J.,Olieric, V.,Wang, M.,Caffrey, M. (deposition date: 2017-02-15, release date: 2017-07-12, Last modification date: 2024-01-17)

Primary citation

Wiktor, M.,Weichert, D.,Howe, N.,Huang, C.Y.,Olieric, V.,Boland, C.,Bailey, J.,Vogeley, L.,Stansfeld, P.J.,Buddelmeijer, N.,Wang, M.,Caffrey, M.
Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis.
Nat Commun, 8:15952-15952, 2017

PubMed 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.

PubMed: 28675161
DOI: 10.1038/ncomms15952

Experimental method

X-RAY DIFFRACTION (2.9 Å)