Penicillin-binding protein (transpeptidase) (PBP)

Penicillin-binding proteins (PBPs) are a family of bacterial enzymes that catalyze the final cross-linking step of peptidoglycan biosynthesis using their transpeptidase activity, which is essential for bacterial cell wall integrity. PBPs are the principal targets of β-lactam antibiotics, which covalently modify the active-site serine, resulting in irreversible inhibition and bacterial death. Multiple PBP isoforms exist in bacteria, fulfilling specialized roles such as endopeptidase, carboxypeptidase, or sensor functions (such as PbpP). Alterations in PBPs, including the acquisition of low-affinity variants, are key determinants of antibiotic resistance in major pathogenic bacteria such as *Staphylococcus aureus* and *Enterococcus* species. PBPs are fundamental in bacterial cell cycle processes, and their disruption leads to cell lysis or aberrant cell division. Targeting PBPs remains a cornerstone of antibacterial therapy, although resistance mechanisms are a growing concern.

Other names

PBPsTranspeptidasesD-alanyl-D-alanine transpeptidase

β-lactam antibiotics: covalent acylation of the active site serine, stably inactivating the transpeptidase and preventing cell wall crosslinking Non-β-lactam inhibitors: competitive inhibition and substrate mimicry