Penicillin-binding protein 3 (PBP3), Penicillin-binding protein 1b (PBP1b), and Penicillin-binding protein 1c (PBP1c) (PBP3/1b/1c)

Penicillin-binding proteins (PBPs) are essential membrane-bound enzymes that catalyze the final steps of peptidoglycan biosynthesis, the primary structural component of the bacterial cell wall [4, 7]. In Gram-negative bacteria, PBP3 (also known as FtsI) is a class B transpeptidase critical for septal peptidoglycan synthesis during cell division, while PBP1b and PBP1c are class A bifunctional enzymes possessing both transglycosylase and transpeptidase activities [2, 8, 12]. PBP1b is a major contributor to cell wall assembly and repair, often working in tandem with PBP3 or PBP1a to maintain structural integrity [12, 15]. These proteins are the primary targets for beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, which act as suicide substrates by covalently binding to the active site serine [1, 10]. Inhibition of these PBPs disrupts cell wall cross-linking, leading to characteristic morphological changes such as filamentation (specifically from PBP3 inhibition) and eventual bacterial cell lysis [4, 14]. Targeting multiple PBPs, particularly the combination of PBP3 and PBP1b, is a key strategy for developing potent antibacterial agents against multi-drug resistant Gram-negative pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae [13, 15]. While PBP1c is often considered non-essential under standard conditions, it remains a target for certain high-affinity carbapenems and may play a role in stress-response-mediated resistance [13, 15].

Other names

FtsImrcBpbpCSeptum formation protein IPenicillin-binding protein 3Penicillin-binding protein 1bPenicillin-binding protein 1cDD-transpeptidaseClass B PBPClass A PBP

Inhibition of the transpeptidase domain of penicillin-binding proteins, preventing the cross-linking of peptidoglycan chains in the bacterial cell wall, leading to cell wall instability, filamentation, and osmotic lysis [1, 4, 7, 10].