Penicillin-binding protein (PBP)

Penicillin-binding proteins (PBPs) are a diverse group of membrane-associated enzymes found in bacteria, characterized by their ability to bind penicillin and other β-lactam antibiotics. PBPs play essential roles in the biosynthesis of peptidoglycan, the main structural component of the bacterial cell wall. They catalyze transglycosylation (polymerization of glycan strands) and transpeptidation (cross-linking between glycan chains). Inhibition of PBPs leads to weakened cell walls and bacterial lysis. PBPs are validated targets for β-lactam antibiotics across many pathogenic bacteria. Mutations or acquisition of alternative low-affinity variants can confer resistance.

β-lactam antibiotics covalently bind to the active site serine residue within PBP’s transpeptidase domain, forming an acyl-enzyme complex that irreversibly inhibits enzymatic activity. This blocks peptidoglycan cross-linking and compromises cell wall integrity.