Penicillin-binding protein 2 and Penicillin-binding protein 3 (PBP2 and PBP3)

Penicillin-binding protein 2 and penicillin-binding protein 3 are essential bacterial enzymes located in the cell membrane, classified as high-molecular-weight transpeptidases (class B PBPs), responsible for critical steps in peptidoglycan synthesis and cell wall cross-linking in most bacteria. These targets are the primary molecular site of action for β-lactam antibiotics, which inhibit their enzyme activity by covalently binding to an active-site serine residue, thereby preventing cell wall assembly and leading to bacterial lysis. PBP2 is particularly important in maintaining the rod shape of Gram-negative bacteria, while PBP3 catalyzes cross-linking during cell division. Resistance often arises via mutations in these proteins, which reduce binding affinity for β-lactams without compromising essential bacterial functions. Both PBP2 and PBP3 are therefore considered validated and high-value therapeutic targets for antibacterial drug design and are integral to efforts in combating drug-resistant bacterial infections.

Other names

PBP2Penicillin-binding protein 2PBP3Penicillin-binding protein 3dd-transpeptidase (functional name, sometimes used)

Covalent binding of β-lactam antibiotics to the active site serine of PBP2/PBP3, inhibiting their transpeptidase activity and blocking cell wall cross-linking, leading to bacterial lysis and death