Penicillin-binding protein 1; Penicillin-binding protein 3 (PBP1; PBP3)

Penicillin-binding proteins are a family of enzymes central to the synthesis and remodeling of bacterial cell walls. They catalyze the transpeptidation reaction that cross-links peptidoglycan polymers, conferring mechanical strength and shape to bacteria. These proteins are the molecular targets of β-lactam antibiotics (such as penicillins and cephalosporins), which covalently bind to their active site serine, inhibiting their enzymatic activity and thus preventing cell wall formation. PBP1 is often a bifunctional enzyme with transglycosylase and transpeptidase domains, while PBP3 is primarily a transpeptidase, both crucial for cell division and morphogenesis. Alterations in PBPs are a common mechanism of antibiotic resistance in clinically important bacteria.

Other names

PBPsClass A Penicillin-binding protein (for PBP1)Class B Penicillin-binding protein (for PBP3)TranspeptidasesPenicillin-binding proteins

Covalent binding of β-lactam ring of antibiotics to the active site serine of PBPs results in enzyme inactivation and blockade of peptidoglycan cross-linking, leading to cell death. Inhibition of transpeptidase activity halts cell wall synthesis, weakening the bacterium and causing lysis.