Penicillin-binding protein 1A and Penicillin-binding protein 1B (PBP1A and PBP1B)

Penicillin-binding protein 1A (PBP1A) and Penicillin-binding protein 1B (PBP1B) are essential high-molecular-weight Class A enzymes involved in the final stages of bacterial peptidoglycan biosynthesis [1, 3]. These bifunctional proteins possess both glycosyltransferase activity, which polymerizes glycan strands, and transpeptidase activity, which cross-links peptide side chains to provide structural integrity to the cell wall [7, 10]. In many bacteria, such as Escherichia coli, PBP1A and PBP1B exhibit functional redundancy; while neither is individually essential, the loss of both is lethal to the cell [11, 14]. PBP1A is typically associated with the elongasome complex for cell wall expansion, whereas PBP1B is often localized to the divisome to facilitate cell division [1, 19]. As the primary targets for beta-lactam antibiotics, these proteins are inhibited when the drug covalently binds to the active-site serine of the transpeptidase domain, leading to cell wall weakening and osmotic lysis [6, 9]. Resistance to these agents frequently develops through mutations in the pbp genes (e.g., ponA, ponB) that reduce antibiotic binding affinity or through the enzymatic degradation of drugs by beta-lactamases [1, 15].

Other names

mrcAmrcBponAponBClass A PBPsBifunctional transglycosylase/transpeptidaseHigh-molecular-weight penicillin-binding proteins

Inhibition of the transpeptidase domain through covalent binding to the active-site serine, preventing peptidoglycan cross-linking, and/or inhibition of the glycosyltransferase domain, preventing glycan strand polymerization.