Penicillin-binding proteins 1A, 1B, 2, 3 (PBPs)

Penicillin-binding proteins (PBPs) 1A, 1B, 2, and 3 are a group of essential bacterial enzymes that catalyze the final stages of peptidoglycan biosynthesis, which provides structural integrity to the bacterial cell wall [2, 3]. PBPs 1A and 1B are high-molecular-weight Class A enzymes that possess bifunctional transglycosylase and transpeptidase activities, whereas PBPs 2 and 3 are Class B enzymes that function as monofunctional transpeptidases involved in cell elongation and septation during division, respectively [3, 8, 9]. These proteins are the primary therapeutic targets for beta-lactam antibiotics, such as penicillins, cephalosporins, and carbapenems, which act as substrate analogs that covalently bind to the active site serine residue, irreversibly inhibiting the enzyme [8, 11]. This inhibition prevents the cross-linking of peptidoglycan strands, resulting in a weakened cell wall that is susceptible to osmotic lysis and subsequent bacterial death [1, 2]. PBPs are central to the mechanism of action of many of the most widely used antimicrobial agents, but their effectiveness is increasingly threatened by the emergence of resistance, often mediated by the production of low-affinity PBP variants or target site mutations [11, 12].

Other names

PBP1APBP1BPBP2PBP3DD-transpeptidasesPeptidoglycan glycosyltransferase/transpeptidaseponAponBpbpAftsImrdAMurein polymerases

Covalent inhibition of the transpeptidase domain by acting as a suicide substrate, preventing the cross-linking of peptidoglycan chains and leading to bacterial cell lysis [8, 11].