Penicillin-binding protein 2x (PBP2x) (PBP2x)

Penicillin-binding protein 2x (PBP2x) is an essential class B high-molecular-weight transpeptidase in Streptococcus pneumoniae, playing a pivotal role in septal peptidoglycan synthesis and bacterial cell division [1, 6, 15]. It is a primary target for beta-lactam antibiotics, which inhibit the enzyme by covalently binding to its active-site serine residue, thereby disrupting cell wall integrity and leading to bacterial lysis [1, 4]. PBP2x is particularly significant as it is often the first target to develop mutations or acquire mosaic gene sequences under the selective pressure of antibiotics like cephalosporins [5, 11]. These structural alterations, such as the common T338A mutation, significantly reduce the enzyme's affinity for drugs, serving as a major mechanism for the development of penicillin-resistant Streptococcus pneumoniae (PRSP) [9, 19]. Because of its central role in both cell viability and antibiotic resistance, PBP2x is a critical biomarker for monitoring drug efficacy and a key focus for the design of novel antimicrobial agents [14, 18].

Other names

pbp2XpbpXPenicillin-binding protein 2XPBP-2XPBP2x

Beta-lactam antibiotics inhibit PBP2x by acting as structural analogs of the D-alanyl-D-alanine substrate, covalently acylating the active-site serine residue to form a stable acyl-enzyme complex that prevents peptidoglycan cross-linking [1, 4, 18].