Bacterial penicillin-binding protein 3 (PBP3)

Bacterial penicillin-binding protein 3 (PBP3), also known as FtsI, is an essential enzyme in many Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa [1, 4]. It is a Class B high-molecular-weight PBP that functions as a DD-transpeptidase, catalyzing the final cross-linking steps of peptidoglycan synthesis specifically at the septum during cell division [2, 9]. Inhibition of PBP3 by antibiotics prevents the formation of the division septum, leading to the characteristic formation of long, non-viable bacterial filaments and eventual cell death [3, 12]. PBP3 is a primary therapeutic target for various beta-lactam antibiotics, most notably the monobactam aztreonam, as well as several cephalosporins and carbapenems [1, 8]. Resistance to these agents is a significant clinical challenge, often mediated by mutations in the ftsI gene that reduce drug binding affinity or by the production of beta-lactamases that hydrolyze the drugs [6, 7]. Related PBPs, such as PBP1a, PBP1b, and PBP2, also play critical roles in cell wall synthesis and maintenance, often serving as co-targets for broad-spectrum beta-lactams [3, 4].

Other names

FtsISeptation protein FtsIDD-transpeptidasePenicillin-binding protein 3PBP-3Peptidoglycan glycosyltransferase / transpeptidase

Inhibition of bacterial peptidoglycan transpeptidation by covalent binding to the active site serine residue, preventing cell wall cross-linking and leading to filamentation and cell lysis.