Escherichia coli penicillin-binding protein 3 (PBP3) (PBP3)

Penicillin-binding protein 3 (PBP3), encoded by the ftsI gene, is an essential transpeptidase in Escherichia coli required for the synthesis of the septal peptidoglycan during cell division (UniProt P0AD68). It belongs to the Class B family of high-molecular-weight PBPs and is localized to the divisome, where it catalyzes the cross-linking of glycan strands to maintain cell wall integrity (PubMed: 25291319). In the context of infectious disease, PBP3 is a critical therapeutic target for several classes of beta-lactam antibiotics, particularly monobactams like aztreonam and third-generation cephalosporins (PubChem CID 5742832). These drugs bind covalently to the active site of PBP3, inhibiting its enzymatic activity and leading to the formation of filamentous bacterial cells that eventually undergo lysis (PubMed: 31653756). Resistance to these treatments is increasingly observed through mutations or specific amino acid insertions in the ftsI gene, which reduce drug affinity and pose a significant challenge in treating multi-drug resistant Gram-negative infections (PubMed: 30201815). Furthermore, PBP3 is often the primary target for newer agents like cefiderocol, which bypasses traditional resistance mechanisms to reach the periplasm (PubMed: 31653756).

Other names

FtsISeptum formation protein FtsIPeptidoglycan glycosyltransferase FtsID-alanyl-D-alanine carboxypeptidasePBP-3

Inhibition of the transpeptidase domain of PBP3, preventing the cross-linking of peptidoglycan subunits during septum formation, which leads to cell filamentation and osmotic lysis (PubMed: 31653756).