Reactive nitrogen species and proteins: biological significance and clinical relevance.

Abstract

Nitric oxide and reactive nitrogen species such as nitrogen dioxide, dinitrogen trioxide and peroxynitrite react selectively with different proteins causing covalent structural modifications that alter protein function (1–3). The predominant post-translational modification mediated by nitric oxide is the S-nitrosylation of cysteine residues whereas reactive nitrogen intermediates primarily oxidize cysteine and nitrate tyrosine residues. Glyceraldehyde-3-phosphate dehydrogenase, ryanodine receptor, p21ras, hemoglobin and caspase 3 are modified by Snitrosylation of cysteine residues in vivo (4–10). The S-nitrosylation of the cysteine residues provides a selective and reversible covalent modification that regulates protein function and explains the ability of nitric oxide to regulate simultaneously different cellular pathways.