Penicillin-binding protein 2a (PBP2a) (PBP2a)

Penicillin-binding protein 2a (PBP2a) is a critical enzyme in Staphylococcus aureus that mediates resistance to nearly all beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Source 1.2.1, 1.3.1). Encoded by the mecA gene, PBP2a is a high-molecular-weight class B transpeptidase that functions as a surrogate for other penicillin-binding proteins (PBPs) when they are inhibited by antibiotics (Source 1.1.2, 1.3.3). Unlike native PBPs, PBP2a possesses a low affinity for most beta-lactams due to a closed active site that is only accessible through allosteric activation or specific high-affinity binding (Source 1.2.3, 1.3.2). This allows the bacterium to continue peptidoglycan cross-linking and maintain cell wall integrity even in the presence of lethal concentrations of traditional antibiotics (Source 1.2.1, 1.2.3). PBP2a is the primary determinant of the methicillin-resistant S. aureus (MRSA) phenotype, making it a major target for specialized anti-MRSA agents like ceftaroline and ceftobiprole (Source 1.3.1, 1.3.3). These drugs are designed to overcome the protein's resistance mechanism by either binding directly to the active site or triggering an allosteric conformational change that opens the site for inhibition (Source 1.2.3, 1.3.1).

Other names

PBP 2'PBP2'mecA proteinPenicillin-binding protein 2'

Inhibition of the transpeptidase activity by covalent acylation of the active-site serine residue (S403), which prevents the cross-linking of peptidoglycan strands in the bacterial cell wall (Source 1.2.1, 1.3.1). Anti-MRSA cephalosporins like ceftaroline also utilize allosteric binding to induce a conformational change that opens the active site for inhibition (Source 1.2.3).