Penicillin-binding protein (PBP) complex (PBP complex)

The Penicillin-binding protein (PBP) complex, also known as the peptidoglycan transpeptidation complex, is a group of essential bacterial enzymes responsible for the final stages of cell wall assembly. These enzymes, specifically DD-transpeptidases, catalyze the formation of cross-links between peptidoglycan strands, which provides the bacterial cell wall with the mechanical strength and rigidity necessary to withstand internal osmotic pressure (StatPearls, 2023). Because this biosynthetic pathway is unique to bacteria and lacks a human counterpart, it is a primary target for many of the most widely used antibiotics. Beta-lactam drugs, such as penicillins and cephalosporins, act by mimicking the D-alanyl-D-alanine terminus of the peptidoglycan precursor, covalently binding to the PBP active site and irreversibly inhibiting its function (NCBI, 2022). This disruption prevents the formation of a stable cell wall, leading to cell wall weakening, autolysis, and bacterial death. Clinical challenges associated with this target include the development of resistance through the production of beta-lactamase enzymes or the acquisition of modified PBPs, such as PBP2a in methicillin-resistant Staphylococcus aureus (MRSA), which have a significantly reduced affinity for these drugs (PubMed, 2021).

Other names

Peptidoglycan transpeptidation/cross-linking complexDD-transpeptidasePeptidoglycan transpeptidasePenicillin-binding proteinsPBP complex

Inhibition of DD-transpeptidase activity by acting as a structural analog of the D-Ala-D-Ala substrate, preventing the cross-linking of peptidoglycan chains.