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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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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
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author Oman, Trent J.
Lupoli, Tania J.
Wang, Tsung-Shing Andrew
Kahne, Daniel
Walker, Suzanne
van der Donk, Wilfred A.
author_facet Oman, Trent J.
Lupoli, Tania J.
Wang, Tsung-Shing Andrew
Kahne, Daniel
Walker, Suzanne
van der Donk, Wilfred A.
author_sort Oman, Trent J.
collection PubMed
description [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.
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spelling pubmed-32064922011-11-02 Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry Oman, Trent J. Lupoli, Tania J. Wang, Tsung-Shing Andrew Kahne, Daniel Walker, Suzanne van der Donk, Wilfred A. J Am Chem Soc [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. American Chemical Society 2011-10-17 2011-11-09 /pmc/articles/PMC3206492/ /pubmed/22003874 http://dx.doi.org/10.1021/ja206281k Text en Copyright © 2011 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Oman, Trent J.
Lupoli, Tania J.
Wang, Tsung-Shing Andrew
Kahne, Daniel
Walker, Suzanne
van der Donk, Wilfred A.
Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
title Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
title_full Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
title_fullStr Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
title_full_unstemmed Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
title_short Haloduracin α Binds the Peptidoglycan Precursor Lipid II with 2:1 Stoichiometry
title_sort haloduracin α binds the peptidoglycan precursor lipid ii with 2:1 stoichiometry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206492/
https://www.ncbi.nlm.nih.gov/pubmed/22003874
http://dx.doi.org/10.1021/ja206281k
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