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Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family
We introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519744/ https://www.ncbi.nlm.nih.gov/pubmed/28729697 http://dx.doi.org/10.1038/s41598-017-06135-w |
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author | Raulinaitis, Vytas Tossavainen, Helena Aitio, Olli Juuti, Jarmo T. Hiramatsu, Keiichi Kontinen, Vesa Permi, Perttu |
author_facet | Raulinaitis, Vytas Tossavainen, Helena Aitio, Olli Juuti, Jarmo T. Hiramatsu, Keiichi Kontinen, Vesa Permi, Perttu |
author_sort | Raulinaitis, Vytas |
collection | PubMed |
description | We introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the overall structure common to the lysostaphin family. Purified LytU lyses S. aureus cells and cleaves pentaglycine, a reaction conveniently monitored by NMR spectroscopy. Substituting the cofactor zinc ion with a copper or cobalt ion remarkably increases the rate of pentaglycine cleavage. NMR and isothermal titration calorimetry further reveal that, uniquely for its family, LytU is able to bind a second zinc ion which is coordinated by catalytic histidines and is therefore inhibitory. The pH-dependence and high affinity of binding carry further physiological implications. |
format | Online Article Text |
id | pubmed-5519744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55197442017-07-26 Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family Raulinaitis, Vytas Tossavainen, Helena Aitio, Olli Juuti, Jarmo T. Hiramatsu, Keiichi Kontinen, Vesa Permi, Perttu Sci Rep Article We introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the overall structure common to the lysostaphin family. Purified LytU lyses S. aureus cells and cleaves pentaglycine, a reaction conveniently monitored by NMR spectroscopy. Substituting the cofactor zinc ion with a copper or cobalt ion remarkably increases the rate of pentaglycine cleavage. NMR and isothermal titration calorimetry further reveal that, uniquely for its family, LytU is able to bind a second zinc ion which is coordinated by catalytic histidines and is therefore inhibitory. The pH-dependence and high affinity of binding carry further physiological implications. Nature Publishing Group UK 2017-07-20 /pmc/articles/PMC5519744/ /pubmed/28729697 http://dx.doi.org/10.1038/s41598-017-06135-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Raulinaitis, Vytas Tossavainen, Helena Aitio, Olli Juuti, Jarmo T. Hiramatsu, Keiichi Kontinen, Vesa Permi, Perttu Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family |
title | Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family |
title_full | Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family |
title_fullStr | Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family |
title_full_unstemmed | Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family |
title_short | Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family |
title_sort | identification and structural characterization of lytu, a unique peptidoglycan endopeptidase from the lysostaphin family |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519744/ https://www.ncbi.nlm.nih.gov/pubmed/28729697 http://dx.doi.org/10.1038/s41598-017-06135-w |
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