Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b

Gonzalez-Delgado, Luz S. ; Walters-Morgan, Hannah ; Salamaga, Bartłomiej ; Robertson, Angus J. LU ; Hounslow, Andrea M. ; Jagielska, Elżbieta ; Sabała, Izabela ; Williamson, Mike P. ; Lovering, Andrew L. and Mesnage, Stéphane (2020) In Nature Chemical Biology 16(1). p.24-30
Abstract
Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine... (More)
Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3b domain, thereby inducing a clustering of SH3b domains. We propose that this unusual binding mechanism allows synergistic and structurally dynamic recognition of S. aureus peptidoglycan and underpins the potent bacteriolytic activity of this enzyme. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Nature Chemical Biology
volume
16
issue
1
pages
24 - 30
publisher
Nature Publishing Group
external identifiers
  • scopus:85074793103
ISSN
1552-4469
DOI
10.1038/s41589-019-0393-4
language
English
LU publication?
no
id
2f44b7d4-ca54-4ea2-87aa-c510fba46f24
date added to LUP
2024-01-25 13:47:02
date last changed
2024-01-26 15:41:45
@article{2f44b7d4-ca54-4ea2-87aa-c510fba46f24,
  abstract     = {{Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3b domain, thereby inducing a clustering of SH3b domains. We propose that this unusual binding mechanism allows synergistic and structurally dynamic recognition of S. aureus peptidoglycan and underpins the potent bacteriolytic activity of this enzyme.}},
  author       = {{Gonzalez-Delgado, Luz S. and Walters-Morgan, Hannah and Salamaga, Bartłomiej and Robertson, Angus J. and Hounslow, Andrea M. and Jagielska, Elżbieta and Sabała, Izabela and Williamson, Mike P. and Lovering, Andrew L. and Mesnage, Stéphane}},
  issn         = {{1552-4469}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{24--30}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Chemical Biology}},
  title        = {{Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b}},
  url          = {{http://dx.doi.org/10.1038/s41589-019-0393-4}},
  doi          = {{10.1038/s41589-019-0393-4}},
  volume       = {{16}},
  year         = {{2020}},
}