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Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans
Staphylococcus simulans biovar staphylolyticus lysostaphin efficiently cleaves Staphylococcus aureus cell walls. The protein is in late clinical trials as a topical anti-staphylococcal agent, and can be used to prevent staphylococcal growth on artificial surfaces. Moreover, the gene has been both st...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286107/ https://www.ncbi.nlm.nih.gov/pubmed/25039253 http://dx.doi.org/10.1111/febs.12929 |
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author | Sabala, Izabela Jagielska, Elzbieta Bardelang, Philip T Czapinska, Honorata Dahms, Sven O Sharpe, Jason A James, Richard Than, Manuel E Thomas, Neil R Bochtler, Matthias |
author_facet | Sabala, Izabela Jagielska, Elzbieta Bardelang, Philip T Czapinska, Honorata Dahms, Sven O Sharpe, Jason A James, Richard Than, Manuel E Thomas, Neil R Bochtler, Matthias |
author_sort | Sabala, Izabela |
collection | PubMed |
description | Staphylococcus simulans biovar staphylolyticus lysostaphin efficiently cleaves Staphylococcus aureus cell walls. The protein is in late clinical trials as a topical anti-staphylococcal agent, and can be used to prevent staphylococcal growth on artificial surfaces. Moreover, the gene has been both stably engineered into and virally delivered to mice or livestock to obtain resistance against staphylococci. Here, we report the first crystal structure of mature lysostaphin and two structures of its isolated catalytic domain at 3.5, 1.78 and 1.26 Å resolution, respectively. The structure of the mature active enzyme confirms its expected organization into catalytic and cell-wall-targeting domains. It also indicates that the domains are mobile with respect to each other because of the presence of a highly flexible peptide linker. The high-resolution structures of the catalytic domain provide details of Zn(2+) coordination and may serve as a starting point for the engineering of lysostaphin variants with improved biotechnological characteristics. STRUCTURED DIGITAL ABSTRACT: lysostaphin by x-ray crystallography (1,2). |
format | Online Article Text |
id | pubmed-4286107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42861072015-01-27 Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans Sabala, Izabela Jagielska, Elzbieta Bardelang, Philip T Czapinska, Honorata Dahms, Sven O Sharpe, Jason A James, Richard Than, Manuel E Thomas, Neil R Bochtler, Matthias FEBS J Implications for Medicine and Pharmacology Staphylococcus simulans biovar staphylolyticus lysostaphin efficiently cleaves Staphylococcus aureus cell walls. The protein is in late clinical trials as a topical anti-staphylococcal agent, and can be used to prevent staphylococcal growth on artificial surfaces. Moreover, the gene has been both stably engineered into and virally delivered to mice or livestock to obtain resistance against staphylococci. Here, we report the first crystal structure of mature lysostaphin and two structures of its isolated catalytic domain at 3.5, 1.78 and 1.26 Å resolution, respectively. The structure of the mature active enzyme confirms its expected organization into catalytic and cell-wall-targeting domains. It also indicates that the domains are mobile with respect to each other because of the presence of a highly flexible peptide linker. The high-resolution structures of the catalytic domain provide details of Zn(2+) coordination and may serve as a starting point for the engineering of lysostaphin variants with improved biotechnological characteristics. STRUCTURED DIGITAL ABSTRACT: lysostaphin by x-ray crystallography (1,2). BlackWell Publishing Ltd 2014-09 2014-08-01 /pmc/articles/PMC4286107/ /pubmed/25039253 http://dx.doi.org/10.1111/febs.12929 Text en Copyright © 2014 Federation of European Biochemical Societies http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Implications for Medicine and Pharmacology Sabala, Izabela Jagielska, Elzbieta Bardelang, Philip T Czapinska, Honorata Dahms, Sven O Sharpe, Jason A James, Richard Than, Manuel E Thomas, Neil R Bochtler, Matthias Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans |
title | Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans |
title_full | Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans |
title_fullStr | Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans |
title_full_unstemmed | Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans |
title_short | Crystal structure of the antimicrobial peptidase lysostaphin from Staphylococcus simulans |
title_sort | crystal structure of the antimicrobial peptidase lysostaphin from staphylococcus simulans |
topic | Implications for Medicine and Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286107/ https://www.ncbi.nlm.nih.gov/pubmed/25039253 http://dx.doi.org/10.1111/febs.12929 |
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