Penicillin-binding protein 1B (Streptococcus pneumoniae) (PBP1B)

Penicillin-binding protein 1B (PBP1B) is a high-molecular-weight, bifunctional enzyme essential for the synthesis of the peptidoglycan layer in the cell wall of Streptococcus pneumoniae (UniProt: P0A4G2). It exhibits both transglycosylase activity, which catalyzes the polymerization of glycan chains, and transpeptidase activity, which facilitates the cross-linking of peptide side chains to provide mechanical strength to the cell wall (PubMed: 10449747). PBP1B is a primary therapeutic target for beta-lactam antibiotics, including penicillins and cephalosporins, which inhibit the enzyme's transpeptidase function (StatPearls: NBK545311). In clinical settings, Streptococcus pneumoniae often develops resistance to these antibiotics through mutations in the pbp1b gene that reduce the affinity of the protein for the drugs (PubMed: 15933035). Understanding the structure and function of PBP1B is crucial for the development of new antimicrobial agents capable of overcoming existing resistance mechanisms in pneumococcal diseases such as pneumonia, meningitis, and sepsis (PubMed: 22412146).

Other names

PBP-1BPBP1bmrcBPeptidoglycan glycosyltransferase/peptidoglycan transpeptidase PBP1BHigh molecular weight penicillin-binding protein 1B

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active site serine of the transpeptidase domain of PBP1B. This acylation inhibits the cross-linking of peptidoglycan strands, leading to a weakened cell wall and subsequent bacterial cell death via osmotic lysis.