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

Penicillin-binding protein 2a (PBP2a) is a specialized transpeptidase enzyme found in methicillin-resistant Staphylococcus aureus (MRSA) that is responsible for bacterial cell wall synthesis (UniProt P0A235). It is encoded by the mecA gene, which is carried on the staphylococcal cassette chromosome mec (SCCmec) (StatPearls, MRSA). The primary biological role of PBP2a is to catalyze the cross-linking of peptidoglycan chains, a process essential for maintaining the structural integrity of the bacterial cell wall (PubMed: 24511202). PBP2a is clinically significant because it possesses a low affinity for most beta-lactam antibiotics, allowing MRSA to survive in environments where native PBPs are inactivated (PubMed: 25197028). Drugs such as ceftaroline and ceftobiprole are specifically designed to target PBP2a by binding to an allosteric site, which triggers a conformational change that enables inhibition of the active site (PubMed: 24511202). Consequently, PBP2a is a major determinant of antibiotic resistance and a key target for developing novel antimicrobial agents against multi-drug resistant staphylococci.

Other names

PBP2'MecAPenicillin-binding protein 2'Transpeptidase PBP2a

Traditional beta-lactam antibiotics fail to inhibit PBP2a due to its closed active site. Anti-MRSA cephalosporins like ceftaroline bind to an allosteric site located approximately 60 Angstroms from the active site; this binding induces a conformational change that opens the active site, allowing a second antibiotic molecule to bind and covalently inhibit the transpeptidase activity, thereby preventing cell wall cross-linking and leading to bacterial cell death (PubMed: 24511202, PubMed: 25197028).