The three-dimensional structure of an arachidonic acid 15-lipoxygenase

Science. 1993 Jun 4;260(5113):1482-6. doi: 10.1126/science.8502991.

Abstract

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 beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Arachidonate 15-Lipoxygenase / chemistry*
  • Arachidonate 15-Lipoxygenase / metabolism
  • Glycine max / enzymology
  • Iron / chemistry
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation

Substances

  • Ligands
  • Iron
  • Arachidonate 15-Lipoxygenase