Interactions of a variety of lipoxygenase inhibitors with a supplementary binding site on soybean lipoxygenase.

Studies on the combined effects of a variety of lipoxygenase inhibitors and cyclo-oxygenase inhibitors revealed strong evidence for the existence of supplementary binding sites on lipoxygenases which modify the reactions of inhibitors with the catalytic site of the enzyme. Independent of their low or non-existent inhibitory reaction at the catalytic site, compounds which interact more effectively with this putative supplementary site are capable of blunting the inhibitory efficacy of potent lipoxygenase inhibitors. Although the degree of interaction with the catalytic site determines the potency of inhibitors, an additional reaction at the supplementary site is also obligatory for inhibitory efficacy. We found that potent lipoxygenase inhibitors possess high affinities for both sites, whereas weak inhibitors and suitable cyclo-oxygenase inhibitors interact predominantly with the supplementary site on the lipoxygenase and possess low or negligible affinities for its catalytic site.