Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family

Abstract 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...

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Autores principales: Vytas Raulinaitis, Helena Tossavainen, Olli Aitio, Jarmo T. Juuti, Keiichi Hiramatsu, Vesa Kontinen, Perttu Permi
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/c8e8573d85a24ba684ea4c55fbb932a8
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spelling oai:doaj.org-article:c8e8573d85a24ba684ea4c55fbb932a82021-12-02T16:08:10ZIdentification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family10.1038/s41598-017-06135-w2045-2322https://doaj.org/article/c8e8573d85a24ba684ea4c55fbb932a82017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06135-whttps://doaj.org/toc/2045-2322Abstract 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.Vytas RaulinaitisHelena TossavainenOlli AitioJarmo T. JuutiKeiichi HiramatsuVesa KontinenPerttu PermiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Vytas Raulinaitis
Helena Tossavainen
Olli Aitio
Jarmo T. Juuti
Keiichi Hiramatsu
Vesa Kontinen
Perttu Permi
Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family
description Abstract 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 article
author Vytas Raulinaitis
Helena Tossavainen
Olli Aitio
Jarmo T. Juuti
Keiichi Hiramatsu
Vesa Kontinen
Perttu Permi
author_facet Vytas Raulinaitis
Helena Tossavainen
Olli Aitio
Jarmo T. Juuti
Keiichi Hiramatsu
Vesa Kontinen
Perttu Permi
author_sort Vytas Raulinaitis
title 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_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_sort identification and structural characterization of lytu, a unique peptidoglycan endopeptidase from the lysostaphin family
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/c8e8573d85a24ba684ea4c55fbb932a8
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