Peptidoglycan D,D-transpeptidase

Peptidoglycan D,D-transpeptidase is an essential bacterial enzyme responsible for catalyzing the final cross-linking step in the synthesis of peptidoglycan—a critical component providing structural strength to the bacterial cell wall. This enzyme forms peptide bonds between adjacent glycan strands by cleaving the terminal D-alanyl-D-alanine bond on one peptide chain and linking it to another peptide unit. The activity is crucial for maintaining cellular shape and protecting bacteria from osmotic lysis. D,D-transpeptidases belong to the penicilloyl-serine transferase superfamily characterized by conserved sequence motifs at their catalytic center. They are mechanistically similar to serine proteases but specialized for transpeptidation rather than hydrolysis. These enzymes are also known as penicillin-binding proteins because they are inhibited by beta-lactam antibiotics such as penicillins and cephalosporins; these drugs mimic natural substrates and irreversibly acylate a key serine residue at the active site. Inhibition of D,D-transpeptidases disrupts peptidoglycan cross-linking, leading to loss of cell wall integrity and ultimately causing bacterial death—making them prime targets for antibiotic therapy against a wide range of pathogenic bacteria including Mycobacterium tuberculosis.[1][3][4][5]

Other names

DD-transpeptidasePenicillin-binding protein (PBP) (when referring to specific family members)FtsI (in Escherichia coli and related species)[5]pbpA (in Mycobacterium tuberculosis)[4]

Inhibition by covalent acylation of the active site serine residue by beta-lactam antibiotics, preventing cross-linking of peptidoglycan strands and leading to bacterial cell lysis due to weakened cell wall integrity[1][3]