Quantitative structure-activity relationships of 6-anilinouracils as inhibitors of Bacillus subtilis DNA polymerase III

Abstract

Quantitative structure-activity relationships of a series of 6-anilinouracil derivatives were developed for their inhibitory activity aganist the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from B. subtilis. Interaction between inhibitors and both enzymes appeared to result solely from hydrophobic binding. Comparison of the substituent contributions indicated increased hydrophobic character and a minor change of shape of the inhibitor binding site of the mutant enzyme. Because the 2 enzymes had identical Km values for substrates, the inhibitor binding site is thought to be distinct from the enzyme active site.