title: Haloduracin α binds the peptidoglycan precursor lipid II with 2:1 stoichiometry.
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.
authors: Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors: Trent J
authors: TJ
authors: Oman
authors: Tania J
authors: TJ
authors: Lupoli
authors: Tsung-Shing Andrew
authors: TS
authors: Wang
authors: Daniel
authors: D
authors: Kahne
authors: Suzanne
authors: S
authors: Walker
authors: Wilfred A
authors: WA
authors: van der Donk
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D013294:Lactococcus lactis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000096:biosynthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010457:Peptidoglycan; C515824:haloduracin, Bacillus halodurans