6RJE

Lysostaphin SH3b P4-G5 complex, homesource dataset

Summary for 6RJE

• Entry DOI: 10.2210/pdb6rje/pdb
• Related: 6rk4
• Descriptor: Lysostaphin, (2~{R})-2-[[(2~{S})-2-[[(4~{R})-5-azanyl-4-[[(2~{S})-2-azanylpropanoyl]amino]-5-oxidanylidene-pentanoyl]amino]-6-[2-[2-[2-[2-(2-azanylethanoylamino)ethanoylamino]ethanoylamino]ethanoylamino]ethanoylamino]hexanoyl]amino]propanoic acid (3 entities in total)
• Functional Keywords: peptidoglycan hydrolase, peptide binding protein
• Biological source: Staphylococcus simulans
• Total number of polymer chains: 1
• Total formula weight: 11940.47

Authors

Walters-Morgan, H.,Lovering, A.L. (deposition date: 2019-04-26, release date: 2019-10-16, Last modification date: 2024-01-24)

Primary citation

Gonzalez-Delgado, L.S.,Walters-Morgan, H.,Salamaga, B.,Robertson, A.J.,Hounslow, A.M.,Jagielska, E.,Sabala, I.,Williamson, M.P.,Lovering, A.L.,Mesnage, S.
Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b.
Nat.Chem.Biol., 16:24-30, 2020

PubMed 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.

PubMed: 31686030
DOI: 10.1038/s41589-019-0393-4

Experimental method

X-RAY DIFFRACTION (2.5 Å)