Penicillin-binding protein 1 and 2 (Staphylococcus aureus) (PBP1/2)

Penicillin-binding proteins 1 and 2 (PBP1 and PBP2) are critical enzymes located on the outer surface of the cytoplasmic membrane in Staphylococcus aureus, where they catalyze the final stages of peptidoglycan assembly (StatPearls, 2023). PBP1 is an essential transpeptidase primarily involved in the formation of the division septum, while PBP2 is a bifunctional enzyme that provides both transglycosylase and transpeptidase activities necessary for the elongation and cross-linking of the cell wall (Pinho et al., 2001). These proteins serve as the primary therapeutic targets for beta-lactam antibiotics, which mimic the D-alanyl-D-alanine substrate to form a stable, covalent acyl-enzyme complex with the active site serine (Bush & Bradford, 2016). This interaction irreversibly inhibits the cross-linking of peptidoglycan chains, resulting in a compromised cell wall structure that cannot withstand internal osmotic pressure, ultimately leading to bacterial autolysis and death (StatPearls, 2023). While these proteins are highly effective targets for traditional penicillins and cephalosporins, the clinical utility of targeting PBP1 and PBP2 is often challenged by the acquisition of the mecA gene, which encodes PBP2a, a variant with low affinity for most beta-lactams that mediates resistance in MRSA strains (Fishovitz et al., 2014). Consequently, understanding the interplay between these native PBPs and their resistant counterparts is essential for the development of next-generation antimicrobial agents (Sauvage et al., 2008).

Other names

PBP1PBP2Penicillin-binding protein 1Penicillin-binding protein 2TranspeptidasePeptidoglycan glycosyltransferase

Covalent inhibition of transpeptidase activity, preventing peptidoglycan cross-linking and leading to bacterial cell lysis.