Penicillin-binding protein 2B (PBP2B) (PBP2B)

Penicillin-binding protein 2B (PBP2B) is an essential transpeptidase in Streptococcus pneumoniae, a major human pathogen responsible for pneumonia, meningitis, and sepsis (UniProt: P0A4G2). It plays a pivotal role in the biosynthesis of the bacterial cell wall by catalyzing the cross-linking of peptidoglycan precursors, specifically during the formation of the division septum (PubMed: 10449737). PBP2B is a primary target for beta-lactam antibiotics, which act as substrate analogs and covalently bind to the active site serine, thereby irreversibly inhibiting the enzyme's activity (StatPearls: NBK541077). The clinical significance of PBP2B is underscored by its role in antibiotic resistance; Streptococcus pneumoniae often acquires mutations in the pbp2b gene through horizontal gene transfer, resulting in mosaic proteins with reduced affinity for penicillins (PubMed: 11053377). These structural alterations allow the bacteria to continue cell wall synthesis even in the presence of therapeutic drug concentrations, posing a significant challenge to current treatment regimens (PubMed: 25155146).

Other names

PBP-2BPenicillin-binding protein 2bpbpXTranspeptidase PBP2BD-alanyl-D-alanine carboxypeptidase

Inhibition of the transpeptidase domain of the protein, which prevents the cross-linking of peptidoglycan chains, leading to cell wall instability and bacterial lysis.