Penicillin-binding protein 2 (PBP2) (PBP2)

Penicillin-binding protein 2 (PBP2) is a high-molecular-weight, class B transpeptidase essential for the synthesis of the peptidoglycan layer in Gram-negative bacteria [1, 3]. It plays a critical role in maintaining the rod-like morphology of cells by catalyzing the cross-linking of peptidoglycan strands during cell elongation [4, 9]. Inhibition of PBP2, typically by beta-lactam antibiotics like mecillinam or carbapenems, leads to the formation of spherical cells (spheroplasts) and eventual bacterial lysis [2, 9]. In many Gram-negative pathogens, PBP2 is a primary target for antimicrobial therapy, and alterations in its structure are a significant mechanism of clinical resistance [5, 8]. Recent drug development has also focused on non-beta-lactam inhibitors, such as diazabicyclooctanes, which specifically target PBP2 to enhance the activity of other antibiotics [7, 16]. This protein is a key component of the elongasome complex, coordinating with other proteins to ensure proper cell wall assembly and structural integrity [10, 15].

Other names

PBP 2mrdApenApbpADD-transpeptidase 2Peptidoglycan glycosyltransferase/transpeptidase PBP2

Irreversible inhibition of the transpeptidase domain through the formation of a covalent acyl-enzyme complex with the active-site serine, which prevents the cross-linking of peptidoglycan strands [2, 14].