Penicillin-binding protein 2; Penicillin-binding protein 3; Penicillin-binding protein 4 (PBP2; PBP3; PBP4)

Penicillin-binding proteins 2, 3, and 4 are members of a family of enzymes responsible for the final steps of bacterial cell wall (peptidoglycan) biosynthesis, specifically the transpeptidation and, in the case of PBP4 also, carboxypeptidation/endopeptidati on reactions necessary for cross-linking glycan chains and maintaining bacterial cell wall integrity. They serve as the molecular targets for β-lactam antibiotics, which inhibit their function by mimicking the natural D-Ala-D-Ala substrate and irreversibly acylating the active site serine residue, thereby preventing proper cell wall formation and resulting in bacterial death. PBP2 and PBP3 belong to class B PBPs and are essential for cell elongation and division, respectively; PBP4 is a class C low-molecular-mass PBP implicated in cell wall maturation and antibiotic resistance.

Other names

PBPsClass B penicillin-binding proteinstranspeptidases (for PBP2 and PBP3)bifunctional PBPsFtsI (PBP3)RodA-PBP2 complex

β-lactam antibiotics covalently bind to the active site serine residue of PBPs, forming an acyl-enzyme complex. This irreversible binding blocks the transpeptidase (and in some cases carboxypeptidase/endopeptidase) activity, thereby inhibiting peptidoglycan cross-linking and disrupting bacterial cell wall synthesis, which ultimately leads to bacterial cell lysis and death.