Penicillin-binding protein class B transpeptidase (Class B PBP)

Penicillin-binding protein (PBP) class B transpeptidases are essential bacterial enzymes responsible for the final stages of peptidoglycan biosynthesis (UniProt, 2023). Unlike Class A PBPs, which possess dual transglycosylase and transpeptidase activities, Class B PBPs are monofunctional enzymes primarily involved in the cross-linking of glycan strands to provide structural integrity to the bacterial cell wall (Nature Reviews Microbiology, 2015). They play specialized roles in bacterial morphogenesis, with specific members like PBP2 and PBP3 (FtsI) being critical for cell elongation and septation during cell division, respectively (PubMed, 2012). These proteins are the primary targets for beta-lactam antibiotics, which mimic the natural D-Ala-D-Ala substrate to acylate the enzyme's active site, leading to cell wall weakening and osmotic lysis (StatPearls, 2023). Resistance to these drugs often arises through mutations in the PBP genes or the acquisition of alternative PBPs with low affinity for antibiotics, such as PBP2a in methicillin-resistant Staphylococcus aureus (MRSA) (CDC, 2019). Understanding the structure and function of Class B PBPs remains vital for the development of next-generation antimicrobial agents to combat multi-drug resistant pathogens.

Other names

Monofunctional transpeptidaseClass B PBPPBP2PBP3FtsIPeptidoglycan D-amino acid transpeptidase

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 to form a stable acyl-enzyme intermediate, thereby irreversibly inhibiting the cross-linking of the bacterial cell wall (StatPearls, 2023).