LIGAND-BINDING AND CATALYTIC PROPERTIES OF RECOMBINANT HUMAN THROMBOXANE SYNTHASE

Abstract

To study the spectrum of modulators of the human thromboxane synthase activity, the interaction of recombinant protein with various low-molecular weight ligands was analyzed. It was shown that thromboxane synthase interacts with a number of fatty acids and their derivatives (potential substrates or concurrent inhibitors), being a target for nonselective inhibition by imidazole and triazole derivatives used in medical practice and agriculture. Thus, another mechanism of action of endocrine-disrupting chemicals (EDC) was established. For the first time, the reduction of heme iron of thromboxane synthase by cytochrome P450 reductase was shown. This interaction accompanied by a partial inhibitory effect on the enzyme suppresses the formation of reaction by-products 12-hydroxyheptadecatenoic acid (12-HHT) and malonic dialdehyde (MDA). It is likely that this mechanism can participate in the regulation of the enzyme activity in vivo.