Fig. 23.23
From: Inhibitors of Hydrolases with an Acyl–Enzyme Intermediate
In the last step of the bacterial cell wall synthesis, a glycopeptide transpeptidase cleaves the bond between two d-Ala–d-Ala groups and forms a new bond between d-Ala and a glycine in a peptidoglycan strand. Lactam antibiotics of the penicillin (23.42–23.44) or cephalosporin type (23.45) can block this step. The penicillin scaffold (green) is reminiscent of the d-Ala–d-Ala group (orange) and is bound analogously by the enzyme. An irreversible inhibition of the transpeptidase is achieved by a nucleophilic opening of the lactam ring with the help of the catalytic serine.