USE OF MODEL ENZYMES IN THE DETERMINATION OF THE MODE OF ACTION OF PENICILLINS AND DELTA-3-CEPHALOSPORINS

The damages caused by penicillins and Δ3-cephalosporins to growing bacteria are related to the ability of these antibiotics to bind to penicillin-binding proteins (PBP) and to inactivate penicillin-sensitive enzymes (PSE). PBP and PSE are membrane bound and are in some cases synonymous. PBP and PSE are members of the bacterial wall peptidoglycan cross-linking system which performs attachment of the nascent peptidoglycan strands to the preexisting wall peptidoglycan. Interactions between PSE and β-lactam antibiotics are interactions between PSE and L-R-D-Ala-D-Ala-terminated substrate analogues which are discussed in some detail. The physiological function of the β-lactam center in PSE is regulatory rather than catalytic; however the postulated effector remains unknown. By interaction the antibiotics impart to the catalytic center a conformation that is incorrect for enzyme action. Inactivation of the wall peptidoglycan cross-linking system causes inhibition of wall synthesis and cessation of cell growth. (Heyrovsky - Prague)