Lipoxygenases are widely distributed dioxygenases whose natural substrates are polyunsaturated fatty acids. These enzymes are responsible for the generation of a number of extraordinarily potent bioactive substances in mammals. The role of lipoxygenases in plants is less well established but they are involved in development and in defense against pests and disease organisms. This study will be focused on soybean lipoxygenase, L-1, the most thoroughly investigated of these enzymes. The goal of the proposed research is to elucidate the structure-function relationship of lipoxygenase. To this end, the X-ray structure of L-1 will be vigorously pursued, following up recent progress. While this work is in progress testing the significance of suggestive amino acid residues and structures will be continued with the aid of recombination genetics and enzymatic studies. A remarkable feature of the lipoxygenase from both the plant and animal kingdoms is the high level amino acid sequence homology in "essential" regions. Insight gained from the proposed studies will be applicable to a broad range of lipoxygenases. Although all lipoxygenases catalyze primarily the formation of hydroperoxides from their substrates, they vary considerably in regio-specificity, substrate specificity, pH optimum and secondary reactions. The proposed studies should provide a basis for understanding these differences. %%% The proposed research should lead to an understanding of the structure-function relationships of the lipoxygenases. These enzymes and their substrates, the common polyunsaturated acids, occur throughout nature. They have been extensively studied in higher plants, as well as more recently in mammals. Lipoxygenase products in mammals are potent effectors of vasoconstriction, chemotaxis and inflammation. In plants, the enzyme controls phytohormone formation and plant defensive systems.
