Inhibition of the RTEM beta-lactamase from Escherichia coli. Interaction of the enzyme with derivatives of olivanic acid.
From chemical and kinetic studies of the interaction of the RTEM beta-lactamase from Escherichia coli with three derivatives of olivanic acid, MM22382 (1), MM13902 (2), and MM4550 (3), a mechanism for the inhibition of the enzyme by these compounds is proposed: the interaction proceeds by formation of an acyl-enzyme, the delta 2-pyrroline, which may either deacylate or undergo tautomerization to the more tightly bound delta 1-pyrroline. The ability of olivanic acids to inhibit the enzyme thus depends on the partitioning of the acyl-enzyme to the delta 1-pyrroline ( a process that competes with the normal hydrolytic pathway) and on the rate of regeneration of free enzyme from this complex.
D000900:Anti-Bacterial Agents; D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli / Q000201:enzymology*; D007769:Lactams; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007769:Lactams; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; C020786:olivanic acid