Peptidoglycan D,D-transpeptidase FtsI (FtsI (also commonly referred to as PBP3))

Peptidoglycan D,D-transpeptidase FtsI is an essential membrane-associated enzyme found in Gram-negative bacteria such as Escherichia coli. It catalyzes the cross-linking step during synthesis of peptidoglycan at the division septum—a critical process for maintaining structural integrity during cell division. As penicillin-binding protein 3 (PBP3), it serves as a primary target for β-lactam antibiotics that disrupt its enzymatic activity by covalent modification, leading to inhibition of bacterial growth and survival. Loss or inhibition of FtsI function results in defective septation and abnormal cellular morphology. Its essential role makes it a key focus both for basic microbiology research on cytokinesis and for clinical development/optimization of antibacterial therapies targeting resistant pathogens.

Other names

Penicillin-binding protein 3PBP3pbpBPeptidoglycan synthase FtsIPeptidoglycan glycosyltransferase 3

Drugs targeting FtsI act primarily by: - Covalently binding to the active site serine residue of the transpeptidase domain. - Inhibiting cross-linking of peptidoglycan strands during cell wall synthesis. This leads to weakened cell walls and ultimately bacterial lysis due to osmotic instability.