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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2011
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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. |
format | Online Article Text |
id | pubmed-3206492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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