Class A penicillin-binding protein (Class A PBP)

Class A penicillin-binding proteins (PBPs) are essential bifunctional enzymes located on the outer surface of the bacterial cytoplasmic membrane, playing a central role in peptidoglycan biosynthesis [1][2]. These proteins possess two distinct catalytic domains: a C-terminal transpeptidase (TP) domain and an N-terminal transglycosylase (TG) domain [3]. The TG domain catalyzes the polymerization of lipid II precursors into glycan chains, while the TP domain facilitates the cross-linking of these chains to provide structural rigidity to the bacterial cell wall [2][4]. Because these processes are vital for bacterial survival and are absent in human cells, Class A PBPs are major targets for antimicrobial therapy [5]. While traditional beta-lactam antibiotics target the TP domain, the TG domain is inhibited by natural products like moenomycin, though no TG-specific inhibitors are currently in widespread clinical use [6]. Disruption of these enzymatic activities leads to cell wall defects, osmotic lysis, and bacterial death, making them indispensable in the treatment of various bacterial infections [1][4].

Other names

Bifunctional penicillin-binding proteinPeptidoglycan glycosyltransferaseMurein polymerasePBP1aPBP1bPBP1c

Inhibition of peptidoglycan polymerization (transglycosylation) and peptide cross-linking (transpeptidation) during bacterial cell wall synthesis.