Penicillin-binding protein 2X (Streptococcus pneumoniae R6) (PBP2X)

Penicillin-binding protein 2X (PBP2X) is an essential high-molecular-weight class B transpeptidase in Streptococcus pneumoniae, with the R6 strain serving as the primary penicillin-sensitive laboratory reference [3, 6, 12]. It is a monofunctional enzyme critical for the synthesis of septal peptidoglycan and is a key component of the divisome machinery required for proper cell division [7, 9, 10]. PBP2X is the primary target for many beta-lactam antibiotics, particularly cephalosporins like cefotaxime, which inhibit the enzyme by acylating its active site serine residue [3, 5, 9]. This inhibition disrupts cell wall integrity, leading to characteristic morphological changes such as "lemon-shaped" cells and eventual bacterial lysis [9]. Resistance to beta-lactams in clinical and laboratory settings is predominantly driven by mutations in the pbp2x gene, such as the T338A substitution, which reduce the protein's affinity for the drug while maintaining its physiological role in cell wall assembly [5, 6, 13]. Furthermore, PBP2X interacts with other proteins, including the Ser/Thr kinase StkP and PBP1a, to coordinate the complex spatial and temporal regulation of pneumococcal morphogenesis [7, 10].

Other names

PBP-2XPenicillin-binding protein 2xpbpXPeptidoglycan transpeptidase 2x

Inhibition of transpeptidase activity by acylating the active site serine residue, leading to defective cell wall synthesis and bacterial lysis.