Integrative structural biology of the penicillin-binding protein-1 from Staphylococcus aureus, an essential component of the divisome machinery

Abstract

Graphical abstract

Penicillin-Binding Protein 1 (PBP1) of Staphylococcus aureus Has Multiple Essential Functions in Cell Division

“…Consequently, and in common with all other PASTA domain structural analyses, the molecular details of PG recognition by Sa PBP1 remain elusive. During the preparation of the manuscript, Martínez-Caballero et al ( 27 ) published a crystal structure of the two PASTA domains of PBP1, also in the absence of endogenous ligand, which is indistinguishable (RMSD, 0.7 Å over 204 superimposed residues) from the structure that we report here. The same authors also solved structures of Sa PBP1 in the presence and absence of β-lactams and pentaglycine (in which the PASTA domains were disordered).…”

“…aureus PBP1 PASTA domains are essential for growth and PBP1 functionality. PBP1 has a short cytoplasmic fragment, a membrane-spanning sequence, an exocytoplasmic N-terminal pedestal domain, and a C-terminal region consisting of the TP domain and two PASTA domains (for penicillin-binding protein and serine/threonine kinase-associated domain) (26,27). We created a set of conditional mutants of pbp1 to investigate the role of PBP1 in cell division and PG synthesis.…”

“…PASTA domains have long been associated with PG binding because of work performed mainly on serine/threonine protein kinases (STPK) ( 26 , 37 – 39 ). Very recently, PBP1 PASTA domains have been shown to bind isolated, small fragments of PG ( 27 ). Therefore, we assessed whether S. aureus PBP1 and its PASTA domains could recognize PG by measuring their affinities for S. aureus cell wall PG with or without WTA (±WTA) with a semiquantitative fluorescence-binding assay and S. aureus PBP1 derivatives produced in Escherichia coli ( Fig.…”