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Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry

[Image: see text] 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 i...

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Detalles Bibliográficos
Autores principales: Oman, Trent J., Lupoli, Tania J., Wang, Tsung-Shing Andrew, Kahne, Daniel, Walker, Suzanne, van der Donk, Wilfred A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2011
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206492/
https://www.ncbi.nlm.nih.gov/pubmed/22003874
http://dx.doi.org/10.1021/ja206281k
Descripción
Sumario:[Image: see text] 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.