Penicillin-binding protein 1A (PBP1A), Penicillin-binding protein 2 (PBP2), Penicillin-binding protein 3 (PBP3) (PBP1A, PBP2, PBP3)

Penicillin-binding proteins (PBPs) are a functionally and structurally related group of membrane-associated enzymes in bacteria that catalyze the final steps of peptidoglycan synthesis for the bacterial cell wall[1][2][3]. PBPs are subdivided by molecular weight and function: Class A PBPs (such as PBP1A) are bifunctional with both glycosyltransferase and transpeptidase activities, critical for peptidoglycan polymerization and cross-linking, while Class B PBPs (such as PBP2 and PBP3) generally function as monofunctional transpeptidases involved in distinct stages of cell elongation and division[2][7]. PBPs are the primary targets of β-lactam antibiotics (e.g., penicillins, cephalosporins), which inhibit these enzymes, leading to death of susceptible bacteria. Mutations or acquisition of variant PBPs with low affinity for β-lactams are a central mechanism of resistance in several clinically important pathogens such as *Streptococcus pneumoniae* and *Escherichia coli*[1][4][7][10]. Additional notes: - PBPs are not found in humans, making them ideal antibacterial targets[3][10]. - Different PBPs may be essential or non-essential depending on bacterial species; in *S. pneumoniae*, PBP1A is essential for viability[4]. - Structural studies reveal PBPs share conserved transpeptidase catalytic mechanisms, typically featuring an active-site serine[7][10]. - PBP profiles and mutations are used clinically to define and track resistance, especially in *S. pneumoniae* and *Staphylococcus aureus*[1][4][7].

Other names

PBPsHigh-molecular-weight PBPs (for PBP1A and PBP2)Monofunctional PBPs (for PBP3)Class A (PBP1A)Class B (PBP2, PBP3)

β-lactam antibiotics bind covalently to the active serine in PBPs, inhibiting transpeptidase activity, blocking peptidoglycan crosslinking and causing cell lysis[7][10].