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

Penicillin-binding protein 2 and penicillin-binding protein 3 are essential bacterial enzymes involved in the biosynthesis and maintenance of the cell wall peptidoglycan layer[2][4][3][1]. They function as transpeptidases, catalyzing the cross-linking of peptidoglycan chains, which provides mechanical strength to the bacterial cell wall and protects against osmotic lysis[2][7]. Both are classified as high-molecular-weight PBPs: PBP2 is primarily involved in elongation and maintenance of rod shape in many Gram-negative bacteria, while PBP3 is especially crucial for septal (division) peptidoglycan cross-linking, facilitating cell division[7][1][3][4]. These proteins are the main targets of β-lactam antibiotics (penicillins, cephalosporins), which bind to their active sites and irreversibly inhibit transpeptidase activity, leading to defective cell wall synthesis and bacterial death[1][2][3][4]. Mutations or structural changes in PBP2 or PBP3 confer resistance to β-lactam antibiotics and pose significant clinical challenges, especially in pathogens such as *Neisseria gonorrhoeae* and *Pseudomonas aeruginosa*[4][9].

Other names

PBP2PBP3High-molecular-weight penicillin-binding protein 2 (sometimes for PBP2)High-molecular-weight penicillin-binding protein 3 (sometimes for PBP3)Transpeptidase (functional classification)

Covalent inhibition of the transpeptidase active site by β-lactam antibiotics, preventing cross-linking of peptidoglycan and causing cell lysis[1][2][3][4]. Drugs mimic the D-alanyl-D-alanine dipeptide substrate and acylate the active site serine residue of the enzyme[2][7].