SUBSTITUTION OF TRYPTOPHAN-165 BY ARGININE IN TEM-1 BETA-LACTAMASE

When tryptophan at position 165 of the TEM-1 beta-lactamase was substituted by an arginine, the mutant enzyme displayed about the same specific activity as the wild-type enzyme. However, alterations of the isoelectric point and of the kinetic constants were observed. The substitution did not result in an increase of the rates of hydrolysis of alpha-carboxypenicillins or cephalosporins as expected, but the mutant enzyme was less susceptible to the inhibitory effect of clavulanic acid, which suggested a possible mechanism of bacterial resistance to beta-lactamase suicide inhibitors.