Penicillin-binding protein 3 (PBP 3) (PBP 3)

Penicillin-binding protein 3 (PBP 3), encoded by the ftsI gene, is an essential transpeptidase in Escherichia coli that plays a critical role in bacterial cell division (UniProt P0AD68). It is a member of the high-molecular-weight class B PBPs and is a key component of the divisome, the protein machinery responsible for synthesizing the septal peptidoglycan (PubMed: 25648178). PBP 3 catalyzes the cross-linking of the peptidoglycan layer, which is vital for the structural integrity of the cell wall during septation. This enzyme is a major therapeutic target for various beta-lactam antibiotics, including monobactams like aztreonam and third-generation cephalosporins like ceftazidime (PubMed: 30249517). When these drugs bind to PBP 3, they inhibit its transpeptidase activity, leading to the formation of long bacterial filaments and eventual cell death through lysis. Resistance to these antibiotics often arises through mutations in the ftsI gene or the production of beta-lactamases that degrade the drugs before they can reach the target (PubMed: 31405878).

Other names

FtsISeptum formation protein ID-alanyl-D-alanine transpeptidasePeptidoglycan glycosyltransferase FtsIPBP-3

Inhibition of the transpeptidase activity of PBP 3, which prevents the cross-linking of peptidoglycan chains during the formation of the division septum, leading to filamentation and eventual bacterial cell lysis (PubMed: 25648178).