The Three-Dimensional Structure of an Arachidonic Acid 15-Lipoxygenase

• DOI: 10.1126/science.8502991
• Publication Date: 2006-10-05T23:05:09Z
• Authors: Jeffrey C. Boyington; Betty J. Gaffney; L. Mario Amzel
• Keywords: Models, Molecular; 0301 basic medicine; 03 medical and health sciences; Glycine max; Protein Conformation; Iron; Molecular Sequence Data; Arachidonate 15-Lipoxygenase; Amino Acid Sequence; Ligands

In mammals, the hydroperoxidation of arachidonic acid by lipoxygenases leads to the formation of leukotrienes and lipoxins, compounds that mediate inflammatory responses. Lipoxygenases are dioxygenases that contain a nonheme iron and are present in many animal cells. Soybean lipoxygenase-1 is a single-chain, 839-residue protein closely related to mammalian lipoxygenases. The structure of soybean lipoxygenase-1 solved to 2.6 angstrom resolution shows that the enzyme has two domains: a 146-residue β barrel and a 693-residue helical bundle. The iron atom is in the center of the larger domain and is coordinated by three histidines and the COO - of the carboxyl terminus. The coordination geometry 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 positions to the surface of the enzyme. The iron, with two adjacent and unoccupied positions, is poised to interact with the 1,4-diene system of the substrate and with molecular oxygen during catalysis.