Penicillin-binding protein 1b and 3 (PBP-1b and PBP-3)

Penicillin-binding proteins (PBPs) are essential bacterial enzymes located in the periplasmic space that catalyze the final stages of peptidoglycan biosynthesis, the primary component of the bacterial cell wall [6, 10]. PBP-1b is a bifunctional Class A enzyme with both transglycosylase and transpeptidase activities, primarily responsible for cell wall elongation and maintaining structural integrity [1, 3, 16]. PBP-3, a Class B monofunctional transpeptidase, is critical for septum formation during bacterial cell division [7, 10, 19]. These proteins are the primary targets of beta-lactam antibiotics, including penicillins, cephalosporins, carbapenems, and monobactams [13, 15]. Drugs bind covalently to the active-site serine of PBPs, inhibiting the cross-linking of peptidoglycan strands, which leads to cell wall weakening, filamentation (specifically with PBP-3 inhibition), and eventual osmotic lysis and cell death [7, 10, 13]. Resistance often arises through the production of beta-lactamases or mutations in the PBP genes that reduce drug affinity [17]. Understanding the specific affinities of antibiotics for different PBPs is crucial for predicting their bactericidal efficacy and morphological effects on bacteria [14].

Other names

MrcBPonAFtsISeptum peptidoglycan synthetaseBifunctional transglycosylase/transpeptidase PBP1bDD-transpeptidase

Inhibition of peptidoglycan transpeptidation by covalent binding to the active-site serine, preventing cell wall cross-linking and leading to bacterial lysis.