Penicillin-binding protein 3 (PBP3) (PBP3)

Penicillin-binding proteins (PBPs) are essential bacterial enzymes involved in the final stages of peptidoglycan synthesis, which is the primary component of the bacterial cell wall [3]. Penicillin-binding protein 3 (PBP3), also known as FtsI, is a transpeptidase specifically required for the formation of the division septum during bacterial cell division; its inhibition leads to the formation of long, non-dividing filaments and eventual cell death [1, 3]. Penicillin-binding proteins 1A and 1B (PBP1A and PBP1B) are high-molecular-weight bifunctional enzymes that possess both transglycosylase and transpeptidase activities, playing a vital role in cell wall elongation and structural integrity [3]. These proteins serve as the primary therapeutic targets for beta-lactam antibiotics, such as monobactams and cephalosporins, which act as substrate analogs to irreversibly inhibit the transpeptidation reaction [2]. Drugs like aztreonam and cefiderocol exhibit high affinity for PBP3, often supplemented by activity against PBP1A/1B to enhance bactericidal efficacy and overcome resistance in Gram-negative pathogens [4, 5]. Understanding the specific binding profile across these PBPs is critical for developing treatments against multi-drug resistant bacteria, particularly those producing metallo-beta-lactamases [4].

Other names

FtsISeptum formation proteinPeptidoglycan D-glutamyl-L-diaminopimelate peptidaseTranspeptidasePBP-3mrcAmrcBPenicillin-binding protein 1APenicillin-binding protein 1B

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active site serine of PBPs. This irreversible inhibition blocks the transpeptidation reaction required for cross-linking peptidoglycan strands, leading to a weakened cell wall, osmotic instability, and bacterial autolysis [2, 3].