Characterization of a tyrosyl radical in prostaglandin endoperoxide synthase-2.
Two different isoforms of prostaglandin H synthase, prostaglandin H synthase-1 and prostaglandin H synthase-2, have been identified. Both isozymes catalyze both cyclooxygenase and peroxidase reactions. Residues identified as being essential for catalysis by ovine prostaglandin endoperoxide H synthase-1 are all conserved in prostaglandin H synthase-2. This suggests that the enzymic reaction mechanisms are fundamentally the same for both isozymes. A tyrosyl radical, which may initiate the cyclooxygenase reaction, is detected by electron paramagnetic resonance spectroscopy after addition of arachidonic acid or hydroperoxides to ovine prostaglandin H synthase-1. We report here that human prostaglandin H synthase-2 also generates a tyrosyl radical centered at g = 2.0040 with a width of 29 gauss, similar to prostaglandin H synthase-1. This is the first spectral evidence that the two isoforms are similar mechanistically.
Hsi
L C
LC
Department of Biochemistry, Michigan State University, East Lansing 48824.
Hoganson
C W
CW
Babcock
G T
GT
Smith
W L
WL
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry*; D018076:DNA, Complementary; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics; D012756:Sheep; D014443:Tyrosine / Q000737:chemistry*
D016861:Cyclooxygenase Inhibitors; D018076:DNA, Complementary; D005609:Free Radicals; D007527:Isoenzymes; D014443:Tyrosine