Penicillin-binding protein 2 and 3 (PBP2 and PBP3) (PBP2/3)

Penicillin-binding proteins (PBPs) are membrane-anchored enzymes essential for the synthesis and remodeling of the bacterial peptidoglycan cell wall [3, 11]. PBP2 and PBP3 are high-molecular-weight class B transpeptidases with specialized roles in bacterial growth: PBP2 is primarily involved in cell wall elongation and maintaining rod shape, while PBP3 (also known as FtsI) is critical for septation during cell division [2, 12]. These proteins are the primary targets of beta-lactam antibiotics, including penicillins, cephalosporins, carbapenems, and monobactams [7, 11]. These drugs act as suicide substrates by forming a stable covalent bond with a catalytic serine residue in the PBP active site, which irreversibly inhibits the transpeptidase activity required for cross-linking peptidoglycan chains [1, 6]. This inhibition leads to structural defects such as filamentation or spherical bulging, eventually causing osmotic lysis and bacterial cell death [3, 4]. Resistance to these antibiotics is a significant clinical challenge, often arising through the production of beta-lactamases or the evolution of PBP variants with reduced drug affinity [6, 13].

Other names

PBP2PBP3Transpeptidase 2Transpeptidase 3FtsImrdARodA-associated PBPSeptal transpeptidaseDD-transpeptidase

Covalent inhibition of the transpeptidase domain via acylation of a catalytic serine residue, which prevents the cross-linking of peptidoglycan strands and leads to bacterial cell lysis [1, 6, 11].