INTERACTIONS BETWEEN ACTIVE-SITE-SERINE BETA-LACTAMASES AND COMPOUNDSBEARING A METHOXY SIDE-CHAIN ON THE ALPHA-FACE OF THE BETA-LACTAM RING - KINETIC AND MOLECULAR MODELING STUDIES

The interactions between three class A beta-lactamases and compounds b earing a methoxy side chain on the alpha-face of the beta-lactam ring (cefoxitin, moxalactam and temocillin) have been studied. When compare d with the situation prevailing with good substrates, both acylation a nd deacylation steps appeared to be severely impaired. Molecular model ling studies of the structures of the Henri-Michaelis complexes and of the acyl-enzymes indicate a major displacement of the crystallographi cally observed water molecule which connects the glutamate-166 and ser ine-70 side chains and underline the role of this water molecule in bo th reaction steps.