Penicillin-Binding Protein 2A (None)

Penicillin-binding protein 2a (PBP2a) is a transpeptidase enzyme that plays a central role in the resistance of methicillin-resistant *Staphylococcus aureus* (MRSA) to β-lactam antibiotics. PBP2a catalyzes the crosslinking of peptidoglycan strands during bacterial cell wall synthesis, even in the presence of β-lactam antibiotics that would normally inhibit this process. Because it is essential for MRSA survival under antibiotic pressure and structurally distinct from human proteins, PBP2a remains an attractive target for novel antibacterial agents.

Other names

PBP2a

PBP2a enables MRSA to survive exposure to β-lactam antibiotics by maintaining cell wall synthesis when other penicillin-binding proteins are inhibited. It does so through its transpeptidase activity, which is essential for crosslinking peptidoglycan chains—a critical step in bacterial cell wall biosynthesis. The active site of PBP2a has a low affinity for most β-lactam antibiotics due to its closed conformation, making it difficult for these drugs to bind and inhibit the enzyme. Allosteric regulation is also involved where the binding of ligands such as muramic acid, peptidoglycan fragments, or certain antibiotics like ceftaroline induces conformational changes that open up the active site