THE 3-DIMENSIONAL STRUCTURE OF AN ARACHIDONIC-ACID 15-LIPOXYGENASE

In mammals, the hydroperoxidation of arachidonic acid by lipoxygenases leads to the formation of leukotrienes and lipoxins, compounds that m ediate inflammatory responses. Lipoxygenases are dioxygenases that con tain a nonheme iron and are present in many animal cells. Soybean lipo xygenase-1 is a single-chain, 839-residue protein closely related to m ammalian lipoxygenases. The structure of soybean lipoxygenase-1 solved to 2.6 angstrom resolution shows that the enzyme has two domains: a 1 46-residue beta barrel and a 693-residue helical bundle. The iron atom is in the center of the larger domain and is coordinated by three his tidines and the COO- of the carboxyl terminus. The coordination geomet ry is nonregular and appears to be a distorted octahedron in which two adjacent positions are not occupied by ligands. Two cavities, in the shapes of a bent cylinder and a frustum, connect the unoccupied positi ons to the surface of the enzyme The iron, with two adjacent and unocc upied positions, is poised to interact with the 1 4-diene system of th e substrate and with molecular oxygen during catalysis.