Nitric oxide: a radical molecule in quest of free radicals in proteins.
A number of enzymes use an amino acid free radical cofactor. Tyrosyl and tryptophanyl radicals react with nitric oxide (NO) with an almost diffusion-limited rate. The catalytically competent tyrosyl radical in ribonucleotide reductase (RR) and prostaglandin H synthase (PGHS) recombines with NO in a radical-radical reaction. The unstable adduct formed can dissociate to regenerate the tyrosyl radical. However, upon prolonged incubation with NO, the diiron center of mouse RR leaks out, while the adduct is successively oxidized into an iminoxyl radical and a nitrotyrosine in PGHS. These data provide a plausible mechanism for the physiological inactivation of RR observed in various models, and may help in understanding the inhibition of PGHS reported in some cases. Reversible combination with NO is an intrinsic property of tyrosyl radicals, which also occurs with Y(D) and Y(Z) in photosystem II, where NO has been useful in the analysis of the oxygen-evolving complex.
Guittet
O
O
Unité 8619, Centre National de la Recherche Scientifique, Université Paris-Sud, Orsay, France.
Roy
B
B
Lepoivre
M
M
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D005609:Free Radicals; D006801:Humans; D007501:Iron / Q000378:metabolism; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D045322:Photosynthetic Reaction Center Complex Proteins / Q000378:metabolism; D045332:Photosystem II Protein Complex; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000596:Amino Acids; D001426:Bacterial Proteins; D005609:Free Radicals; D009566:Nitrates; D045322:Photosynthetic Reaction Center Complex Proteins; D045332:Photosystem II Protein Complex; D011506:Proteins; C039642:peroxynitric acid; D016718:Arachidonic Acid; D009569:Nitric Oxide; D014443:Tyrosine; D007501:Iron; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases