Penicillin-binding protein 1A and 1B (PBP1A/1B)

Penicillin-binding proteins (PBPs) are essential bacterial enzymes involved in the assembly and maintenance of the peptidoglycan layer, which provides structural integrity to the cell wall (UniProt, 1.1.3). PBP1A and PBP1B are high-molecular-weight Class A PBPs that exhibit bifunctional activity, combining transglycosylase and transpeptidase domains to polymerize and cross-link glycan strands (NIH, 1.4.1; UniProt, 1.2.5). These proteins are the primary targets of beta-lactam antibiotics, which act as substrate analogs to inhibit the transpeptidase reaction (Medscape, 1.3.3). Inhibition of PBP1A and PBP1B disrupts cell wall synthesis, making the bacteria susceptible to osmotic pressure and leading to cell lysis (Wikipedia, 1.3.2). While often redundant in function, these proteins can have specialized roles in cell division and elongation depending on the bacterial species (NIH, 1.5.3). Resistance to antibiotics often arises through mutations in these proteins that decrease their affinity for drugs, posing a significant challenge in treating infections caused by multi-drug resistant pathogens (Contagion Live, 1.5.4).

Other names

Penicillin-binding protein 1aPenicillin-binding protein 1bmrcAmrcBponAponBBifunctional transglycosylase/transpeptidaseMurein polymerase

Beta-lactam antibiotics covalently bind to the active site of the transpeptidase domain of PBPs, mimicking the D-alanyl-D-alanine substrate (Medscape, 1.3.3). This inhibition prevents the cross-linking of peptidoglycan strands, weakening the bacterial cell wall and leading to osmotic lysis and cell death (Wikipedia, 1.3.2).