Peptidoglycan transpeptidase enzyme

Peptidoglycan transpeptidase enzymes, commonly known as penicillin-binding proteins (PBPs), are essential bacterial enzymes that catalyze the final cross-linking step in cell wall peptidoglycan biosynthesis[1][2][3][8]. These serine-type transpeptidases are characterized by their ability to form covalent enzyme-substrate intermediates via a conserved SxxK motif at the active site, which facilitates peptide bond formation between adjacent glycan chain peptides[2][3]. The integrity and strength of the bacterial cell wall depend on these peptide cross-links, and inhibition of PBPs disrupts cell wall synthesis, ultimately causing bacterial cell death and lysis[1][4]. PBPs are the primary molecular targets of β-lactam antibiotics, making them a central therapeutic target in bacterial infection management[1][2][3]. Variations in PBP structure and expression underlie important mechanisms of antibiotic resistance, such as methicillin resistance in Staphylococcus aureus (MRSA)[2]. There are multiple PBP classes (A, B, C), distinguished by domain structure and function, and similar transpeptidase activity also exists in related families such as LD-transpeptidases[2][7]. Therapeutic challenges include the rapid evolution of resistance and the need for specific biomarkers to guide antibiotic selection.

Other names

penicillin-binding protein (PBP)DD-transpeptidasebacterial transpeptidasecell wall transpeptidase

Inhibition via covalent acylation of active-site serine by β-lactam antibiotics; Blocking of peptidoglycan cross-linking, resulting in cell wall defects and lysis