Penicillin-binding protein 1-4 (PBP1-4)

Penicillin-binding proteins (PBPs) are a group of essential bacterial enzymes involved in the final stages of peptidoglycan biosynthesis, which is the primary component of the bacterial cell wall (StatPearls, 2023). These proteins, including PBPs 1, 2, 3, and 4, function as transpeptidases, carboxypeptidases, and endopeptidases to catalyze the cross-linking of glycan strands and the remodeling of the cell wall during growth and division (UniProt, 2024). PBPs are the definitive targets for beta-lactam antibiotics, which include penicillins, cephalosporins, carbapenems, and monobactams (PubMed, 2008). By binding covalently to the active site of these enzymes, the drugs inhibit the formation of a stable cell wall, resulting in osmotic lysis and bacterial death (StatPearls, 2023). Resistance to these drugs often arises through the modification of PBPs, such as the acquisition of low-affinity variants like PBP2a in methicillin-resistant Staphylococcus aureus (MRSA) (PubMed, 2015). Consequently, PBPs remain a central focus in the development of novel antimicrobial therapies designed to circumvent existing resistance mechanisms.

Other names

PBPsDD-transpeptidaseDD-carboxypeptidasePeptidoglycan glycosyltransferaseMurein hydrolase

Beta-lactam antibiotics act as substrate analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active-site serine of penicillin-binding proteins (PBPs). This inhibition prevents the transpeptidation reaction required for cross-linking peptidoglycan chains, leading to cell wall defects and bacterial lysis (StatPearls, 2023).