Penicillin-binding protein II (PBP2 (for Penicillin-binding protein II), PBP3 (for Penicillin-binding protein III))

Penicillin-binding proteins II and III are essential **bacterial enzymes** involved in the final stages of **cell wall peptidoglycan synthesis**, specifically catalyzing the cross-linking of glycan chains through their **transpeptidase activity**. These proteins are found on the inner membrane of bacteria and are critical for maintaining cell shape and integrity. They serve as primary targets for β-lactam antibiotics such as penicillins and cephalosporins. Inhibition by these drugs occurs via covalent binding to an active site serine residue within a conserved SXXK motif, blocking enzymatic function necessary for bacterial growth and division[1][2][3]. For example, inhibition of PBP3 leads to filamentous growth due to failed cell separation during division[5]. Resistance can arise through mutations that alter drug binding or expression of alternative PBPs with reduced affinity for β-lactams.\n\nNote on nomenclature: "Penicillin-binding protein II/III" refers collectively to two related but distinct enzymes—PBP2 is typically associated with maintenance of rod shape during elongation; PBP3 is essential for septum formation during cell division. Both are considered high-molecular-mass class B PBPs with similar domain structures but distinct physiological roles depending on species context[1][5].

Other names

PBP2PBP3ftsI (gene encoding PBP3 in Escherichia coli and other bacteria)penicillin-sensitive transpeptidase

Covalent acylation of the active site serine by β-lactam antibiotics inhibits the transpeptidase activity required for peptidoglycan cross-linking in bacterial cell walls[1][2][3].\n - This leads to impaired cell wall synthesis and ultimately bacterial lysis.