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Updated: May 28, 2026

Enrichment of Bacterial Lipoproteins and Preparation of N-terminal Lipopeptides for Structural Determination by Mass Spectrometry
Published on: May 21, 2018
Haloduracin α binds the peptidoglycan precursor lipid II with 2:1 stoichiometry
Trent J Oman1, Tania J Lupoli, Tsung-Shing Andrew Wang
1Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
Abstract:
The two-peptide lantibiotic haloduracin is composed of two post-translationally modified polycyclic peptides that synergistically act on gram-positive bacteria. We show here that Halα inhibits the transglycosylation reaction catalyzed by PBP1b by binding in a 2:1 stoichiometry to its substrate lipid II. Halβ and the mutant Halα-E22Q were not able to inhibit this step in peptidoglycan biosynthesis, but Halα with its leader peptide still attached was a potent inhibitor. Combined with previous findings, the data support a model in which a 1:2:2 lipid II:Halα:Halβ complex inhibits cell wall biosynthesis and mediates pore formation, resulting in loss of membrane potential and potassium efflux.
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