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Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence
Streptococcus pneumoniae is a major cause of life-threatening diseases worldwide. Here we provide an in-depth functional characterization of LytB, the peptidoglycan hydrolase responsible for physical separation of daughter cells. Identified herein as an N-acetylglucosaminidase, LytB is involved also...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633669/ https://www.ncbi.nlm.nih.gov/pubmed/26537571 http://dx.doi.org/10.1038/srep16198 |
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author | Rico-Lastres, Palma Díez-Martínez, Roberto Iglesias-Bexiga, Manuel Bustamante, Noemí Aldridge, Christine Hesek, Dusan Lee, Mijoon Mobashery, Shahriar Gray, Joe Vollmer, Waldemar García, Pedro Menéndez, Margarita |
author_facet | Rico-Lastres, Palma Díez-Martínez, Roberto Iglesias-Bexiga, Manuel Bustamante, Noemí Aldridge, Christine Hesek, Dusan Lee, Mijoon Mobashery, Shahriar Gray, Joe Vollmer, Waldemar García, Pedro Menéndez, Margarita |
author_sort | Rico-Lastres, Palma |
collection | PubMed |
description | Streptococcus pneumoniae is a major cause of life-threatening diseases worldwide. Here we provide an in-depth functional characterization of LytB, the peptidoglycan hydrolase responsible for physical separation of daughter cells. Identified herein as an N-acetylglucosaminidase, LytB is involved also in colonization and invasion of the nasopharynx, biofilm formation and evasion of host immunity as previously demonstrated. We have shown that LytB cleaves the GlcNAc-β-(1,4)-MurNAc glycosidic bond of peptidoglycan building units. The hydrolysis occurs at sites with fully acetylated GlcNAc moieties, with preference for uncross-linked muropeptides. The necessity of GlcN acetylation and the presence of a single acidic moiety (Glu585) essential for catalysis strongly suggest a substrate-assisted mechanism with anchimeric assistance of the acetamido group of GlcNAc moieties. Additionally, modelling of the catalytic region bound to a hexasaccharide tripentapeptide provided insights into substrate-binding subsites and peptidoglycan recognition. Besides, cell-wall digestion products and solubilisation rates might indicate a tight control of LytB activity to prevent unrestrained breakdown of the cell wall. Choline-independent localization at the poles of the cell, mediated by the choline-binding domain, peptidoglycan modification, and choline-mediated (lipo)teichoic-acid attachment contribute to the high selectivity of LytB. Moreover, so far unknown chitin hydrolase and glycosyltransferase activities were detected using GlcNAc oligomers as substrate. |
format | Online Article Text |
id | pubmed-4633669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46336692015-11-05 Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence Rico-Lastres, Palma Díez-Martínez, Roberto Iglesias-Bexiga, Manuel Bustamante, Noemí Aldridge, Christine Hesek, Dusan Lee, Mijoon Mobashery, Shahriar Gray, Joe Vollmer, Waldemar García, Pedro Menéndez, Margarita Sci Rep Article Streptococcus pneumoniae is a major cause of life-threatening diseases worldwide. Here we provide an in-depth functional characterization of LytB, the peptidoglycan hydrolase responsible for physical separation of daughter cells. Identified herein as an N-acetylglucosaminidase, LytB is involved also in colonization and invasion of the nasopharynx, biofilm formation and evasion of host immunity as previously demonstrated. We have shown that LytB cleaves the GlcNAc-β-(1,4)-MurNAc glycosidic bond of peptidoglycan building units. The hydrolysis occurs at sites with fully acetylated GlcNAc moieties, with preference for uncross-linked muropeptides. The necessity of GlcN acetylation and the presence of a single acidic moiety (Glu585) essential for catalysis strongly suggest a substrate-assisted mechanism with anchimeric assistance of the acetamido group of GlcNAc moieties. Additionally, modelling of the catalytic region bound to a hexasaccharide tripentapeptide provided insights into substrate-binding subsites and peptidoglycan recognition. Besides, cell-wall digestion products and solubilisation rates might indicate a tight control of LytB activity to prevent unrestrained breakdown of the cell wall. Choline-independent localization at the poles of the cell, mediated by the choline-binding domain, peptidoglycan modification, and choline-mediated (lipo)teichoic-acid attachment contribute to the high selectivity of LytB. Moreover, so far unknown chitin hydrolase and glycosyltransferase activities were detected using GlcNAc oligomers as substrate. Nature Publishing Group 2015-11-05 /pmc/articles/PMC4633669/ /pubmed/26537571 http://dx.doi.org/10.1038/srep16198 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Rico-Lastres, Palma Díez-Martínez, Roberto Iglesias-Bexiga, Manuel Bustamante, Noemí Aldridge, Christine Hesek, Dusan Lee, Mijoon Mobashery, Shahriar Gray, Joe Vollmer, Waldemar García, Pedro Menéndez, Margarita Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence |
title | Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence |
title_full | Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence |
title_fullStr | Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence |
title_full_unstemmed | Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence |
title_short | Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence |
title_sort | substrate recognition and catalysis by lytb, a pneumococcal peptidoglycan hydrolase involved in virulence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633669/ https://www.ncbi.nlm.nih.gov/pubmed/26537571 http://dx.doi.org/10.1038/srep16198 |
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