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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
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).
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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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