Penicillin-binding protein 1A, 1B, and 3 (PBP 1A, 1B, and 3) (PBPs 1A, 1B, and 3)

Penicillin-binding proteins (PBPs) 1A, 1B, and 3 are essential bacterial enzymes located on the outer surface of the cytoplasmic membrane, where they catalyze the final stages of peptidoglycan cell wall synthesis [1, 23]. PBPs 1A and 1B are high-molecular-weight Class A bifunctional enzymes possessing both transglycosylase activity, which polymerizes glycan strands, and transpeptidase activity, which cross-links peptide side chains [23, 27]. PBP3, also known as FtsI in many Gram-negative species, is a Class B transpeptidase specifically required for the formation of the division septum during bacterial replication [1, 27]. These proteins are the primary therapeutic targets for beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [11, 24]. These drugs act as substrate analogs that covalently bind to the active-site serine of the transpeptidase domain, forming a stable acyl-enzyme complex that irreversibly inhibits the enzyme [18, 20]. The resulting failure to maintain cell wall integrity leads to morphological changes, such as filamentation or spheroplast formation, and ultimately results in bacterial cell lysis and death [1, 26]. Resistance to these drugs often arises through the acquisition of low-affinity PBP variants or the production of beta-lactamases that degrade the antibiotics before they reach their targets [20, 24]. Understanding the specific binding affinities of different antibiotics for these PBPs is crucial for developing effective treatments against multi-drug resistant bacterial pathogens [22, 24].

Other names

PBP1APBP1BPBP3MrcAMrcBFtsIponAponBftsIPeptidoglycan synthase 1APeptidoglycan synthase 1BSeptum-forming transpeptidase

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors [11, 18]. They covalently bind to the active-site serine residue of the transpeptidase domain of PBPs, forming a stable acyl-enzyme complex [1, 20]. This irreversible inhibition prevents the cross-linking of peptidoglycan strands, leading to a weakened cell wall, osmotic instability, and eventual bacterial cell lysis [11, 26].