Chemical Considerations and Biological Selectivity of Protein Nitrosation: Implications for NO-Mediated Signal Transduction

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Abstract
Nitric oxide (NO) is a diatomic free radical that plays an important role in the homeostatic regulation of the central nervous, immune, and cardiovascular systems. In addition to its interaction with guanylate cyclase, which results in the production of the second messenger cyclic GMP, there is now a large body of literature indicating that many of the effects associated with the production of NO are due to the nitrosation of cysteine residues in proteins. In this review, we outline the primary chemical pathways that may account for protein nitrosation in cells and tissues. The functional implications of protein nitrosation are discussed by using the p21ras subfamily of small monomeric GTPases and the cysteine-containing aspartate-specific proteases (caspases) as prototypical examples. Overall, in addition to the well characterized NO/O2 reaction, there may exist multiple pathways accounting for protein nitrosation in cells. These include acid- and free radical-mediated mechanisms. Although protein nitrosation may not be limited to cysteine residues, there is now ample evidence that nitrosation reactions, in a fashion similar to oxidative modifications, may modulate the structure, activity, association, and localization of a specific subset of proteins in cells and tissues. Antioxid. Redox Signal. 7, 593–606.