A protein radical and ferryl intermediates are generated by linoleate diol synthase, a ferric hemeprotein with dioxygenase and hydroperoxide isomerase activities

J Biol Chem. 1998 Aug 14;273(33):20744-51. doi: 10.1074/jbc.273.33.20744.

Abstract

Linoleate diol synthase (LDS) was isolated as a hemeprotein from the fungus Gaeumannomyces graminis. LDS converts linoleate sequentially to 8R-hydroperoxylinoleate (8-HPODE) through an 8-dioxygenase by insertion of molecular oxygen and to 7S,8S-dihydroxylinoleate through a hydroperoxide isomerase by intramolecular oxygen transfer. Light absorption and EPR spectra of LDS indicated that the heme iron was ferric and mainly high spin. Oxygen consumption during catalysis started after a short time lag which was reduced by 8-HPODE. Catalysis declined due to suicide inactivation. Stopped flow studies with LDS and 8-HPODE at 13 degreesC showed a rapid decrease in light absorption at 406 nm within 35 ms with a first order rate constant of 90-120 s-1. Light absorption at 406 nm then increased at a rate of approximately 4 s-1, whereas the absorption at 421 nm increased after a lag time of approximately 5 ms at a rate of approximately 70 s-1. EPR spectra at 77 K of LDS both with linoleic acid and 8-HPODE showed a transient doublet when quenched after incubation on ice for 3 s (major hyperfine splitting 2.3 millitesla; g = 2.005), indicating a protein radical. The relaxation properties of the protein radical suggested interaction with a metal center. 8-HPODE generated about twice as much radical as linoleic acid, and the 8-HPODE-induced radical appeared to be stable. Our results suggest that LDS may form, in analogy with prostaglandin H synthases, ferryl intermediates and a protein radical during catalysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electron Spin Resonance Spectroscopy
  • Enzyme Activation
  • Ferric Compounds / chemistry
  • Free Radicals
  • Glutathione Peroxidase / chemistry
  • Hemeproteins / chemistry*
  • Hydrogen Peroxide / chemistry
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / chemistry*
  • Intramolecular Oxidoreductases / metabolism
  • Kinetics
  • Light
  • Oxygenases / antagonists & inhibitors
  • Oxygenases / chemistry*
  • Oxygenases / metabolism
  • Prostaglandin-Endoperoxide Synthases / chemistry*
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • Ferric Compounds
  • Free Radicals
  • Hemeproteins
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Oxygenases
  • Prostaglandin-Endoperoxide Synthases
  • Intramolecular Oxidoreductases
  • hydroperoxide isomerase