Penicillin-binding protein 2 (Staphylococcus aureus) (PBP2)

Penicillin-binding protein 2 (PBP2) is a critical bifunctional enzyme in Staphylococcus aureus responsible for the assembly of the bacterial cell wall [1]. It catalyzes both the polymerization of glycan strands (transglycosylation) and the cross-linking of peptide side chains (transpeptidation) within the peptidoglycan layer [2]. This structural integrity is vital for bacterial survival against osmotic pressure. PBP2 is a primary target for beta-lactam antibiotics, which act as substrate analogs and form a stable covalent acyl-enzyme complex with the active site serine [3]. This binding halts cell wall synthesis and ultimately leads to bacterial lysis. In the context of clinical resistance, the emergence of methicillin-resistant S. aureus (MRSA) is primarily due to the acquisition of PBP2a, a low-affinity homolog that can function when native PBP2 is inhibited [4]. Consequently, PBP2 remains a focal point for the study of antibiotic efficacy and the development of next-generation carbapenems and cephalosporins [5].

Other names

PBP-2Peptidoglycan glycosyltransferase/transpeptidase PBP2pbpBPenicillin-binding protein 2 (S. aureus)

Inhibition of bacterial cell wall synthesis by covalent binding to the active site serine residue, which prevents the transpeptidation reaction required for peptidoglycan cross-linking.