Penicillin-binding protein 1A and Penicillin-binding protein 2X (Streptococcus pneumoniae) (PBP1A/PBP2X)

Penicillin-binding proteins 1A (PBP1A) and 2X (PBP2X) are essential enzymes in Streptococcus pneumoniae responsible for the final stages of peptidoglycan synthesis, the primary component of the bacterial cell wall [4, 12]. PBP1A is a bifunctional class A protein with both transglycosylase and transpeptidase activities, while PBP2X is a monofunctional class B transpeptidase specifically required for septal cross-wall formation during cell division [1, 13, 18]. These proteins are the primary targets for beta-lactam antibiotics, such as penicillins and cephalosporins, which act as suicide inhibitors by covalently binding to the active site serine [11, 14]. Resistance to these drugs in clinical isolates typically arises through the acquisition of mosaic PBP genes via horizontal gene transfer, which encode variants with reduced affinity for the antibiotics [12, 19]. Understanding the structural and functional roles of PBP1A and PBP2X is critical for developing new therapeutic strategies against multidrug-resistant pneumococcal infections [13, 15].

Other names

PBP1APBP2XPenicillin-binding protein 1aPenicillin-binding protein 2xStreptococcus pneumoniae PBP1AStreptococcus pneumoniae PBP2Xpbp1apbp2x

Inhibition of peptidoglycan transpeptidation by covalent acylation of the active-site serine residue, leading to cell wall instability and bacterial lysis.