PS-5 inhibition of a beta-lactamase from Proteus vulgaris.
Inhibition of Proteus vulgaris beta-lactamase by a new beta-lactam antibiotic, PS-5 was studied kinetically. There were two stages of inhibition. In the early stage, PS-5 inhibited the beta-lactamase by formation of a Michaelis-complex, and showed a competitive inhibition pattern with Ki-value of 0.22 microM (substrate, cephaloridine). After the formation of a Michaelis-complex between PS-5 and the enzyme, PS-5 showed a characteristic progressive inhibition pattern with time. Maximum inactivation was obtained after several minutes of preincubation of the enzyme with PS-5; as hydrolysis of PS-5 progressed, the enzyme activity was gradually recovered. Reactivation by an excess of substrate (cephaloridine) was not substantially realized in the presence of PS-5. PS-5 was very slowly hydrolyzed by the enzyme, showing a triphasic pattern in its reaction curve.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002509:Cephaloridine / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D011514:Proteus vulgaris / Q000201:enzymology*; D013053:Spectrophotometry; D013845:Thienamycins; D013997:Time Factors; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; C016883:PS 5; D002509:Cephaloridine