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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Gonzalez-Delgado LS,Walters-Morgan H,Salamaga B,Robertson AJ,Hounslow AM,Jagielska E,Sabała I,Williamson MP,Lovering AL,Mesnage Sdoi
10.1038/s41589-019-0393-4subject
Has Abstractpub_date
2020-01-01 00:00:00pages
24-30issue
1eissn
1552-4450issn
1552-4469pii
10.1038/s41589-019-0393-4journal_volume
16pub_type
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