Penicillin-binding protein 1A (PBP1A) (PBP1A)

Penicillin-binding protein 1A (PBP1A) is a high-molecular-weight, bifunctional enzyme essential for the synthesis and maintenance of the peptidoglycan layer in the Escherichia coli cell wall (UniProt: P02918). It possesses both transglycosylase activity, which polymerizes glycan chains, and transpeptidase activity, which cross-links these chains to provide structural integrity (PubMed: 21422258). As a primary target for beta-lactam antibiotics, PBP1A plays a critical role in bacterial survival; its inhibition leads to cell wall defects and eventual lysis (PubMed: 15130103). In the context of infection, PBP1A is a validated therapeutic target for treating various E. coli-mediated conditions, including urinary tract infections and sepsis (StatPearls}

Other names

PBP-1aMurein polymerase 1AmrcAponAPeptidoglycan synthase 1ABifunctional penicillin-binding protein 1A

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of the peptidoglycan precursor. They covalently bind to the active site serine of the transpeptidase domain of PBP1A, forming a stable acyl-enzyme intermediate. This inhibition prevents the cross-linking of peptidoglycan chains, leading to a weakened cell wall and subsequent osmotic lysis of the bacterium (PubMed: 15130103).