Penicillin-binding protein 1a and Penicillin-binding protein 3 (Escherichia coli) (PBP-1a and PBP-3)

Penicillin-binding proteins (PBPs) are essential enzymes in Escherichia coli that catalyze the final steps of peptidoglycan synthesis, a critical component of the bacterial cell wall (UniProt P02918, P0AD68). PBP-1a (encoded by mrcA) is a high-molecular-weight class A PBP with bifunctional glycosyltransferase and transpeptidase activities, primarily involved in cell wall elongation and maintenance (NIH PMC2168647). PBP-3 (encoded by ftsI), a class B PBP, is a specialized transpeptidase essential for the formation of the division septum during cytokinesis (PubMed 24875388). These proteins are the primary targets for beta-lactam antibiotics, which covalently bind to the active-site serine residue, inhibiting the cross-linking of peptidoglycan chains (StatPearls NBK545311). Inhibition of PBP-1a typically results in rapid cell lysis, whereas inhibition of PBP-3 leads to the formation of long, non-dividing filaments and eventual cell death (PubMed 15522102). Resistance to drugs targeting these proteins can arise through mutations, such as amino acid insertions in PBP-3, which reduce antibiotic affinity while maintaining enzymatic function (NIH PMC10000134).

Other names

PBP1aPBP3mrcAftsIponApbpBPeptidoglycan glycosyltransferase/transpeptidase PBP1aPeptidoglycan D-alanine transpeptidase PBP3Septum formation protein I

Beta-lactam antibiotics act as substrate analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active-site serine of PBPs to inhibit their transpeptidase activity, thereby preventing cell wall cross-linking and leading to bacterial lysis.