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

Penicillin-binding protein 3 (PBP3), also known as FtsI, is an essential enzyme in Escherichia coli required for the synthesis of the division septum during bacterial cytokinesis (UniProt P0AD68). It is a bitopic membrane protein with a large periplasmic domain that possesses transpeptidase activity, responsible for cross-linking peptidoglycan strands to ensure cell wall stability (PubMed: 31615864). Inhibition of PBP3 by antibiotics prevents the formation of a functional septum, causing the bacteria to grow into long filaments that eventually undergo lysis (StatPearls: Beta-Lactam Antibiotics). PBP3 is a major clinical target for various beta-lactam antibiotics, including monobactams like aztreonam and cephalosporins like ceftazidime, which mimic the D-Ala-D-Ala substrate to covalently bind and inactivate the enzyme (PubChem: Aztreonam). Resistance mechanisms often involve amino acid substitutions in the transpeptidase domain of PBP3, such as the N346S or F533L mutations, which reduce drug affinity while maintaining sufficient enzymatic activity for bacterial survival (PubMed: 33431424).

Other names

FtsISeptation protein FtsIPeptidoglycan glycosyltransferase/transpeptidase PBP3D-alanyl-D-alanine carboxypeptidase

Inhibition of the transpeptidase domain of PBP3 prevents the cross-linking of peptidoglycan precursors during cell wall synthesis, specifically at the division septum, leading to filamentation and osmotic lysis of the bacterium (StatPearls: Beta-Lactam Antibiotics).