Nitration and Nitrosylation
The S-nitrosylation reaction of cysteine residues is a chemical modication considered similar to oxidation as a regulatory process19-22 similar to cysteine sulfenic acid23 and sulfhydration.24 Sulfhydration is the process of hydrogen sulde modication of the cysteine thiol group to form a persulde; hydrogen sulde has been compared to nitric oxide as a regulatory factor.25 The formation of Snitrosocysteine in proteins can proceed to the formation of cystine26 as observed with cysteine sulfenic acid.27 The formation of disulde and mixed disulde bonds following S-nitrosylation is discussed in the succeeding text. In vivo nitrosylation occurs through nitric oxide, originally described as endothelial-derived relaxing factor28 derived from arginine. The reaction of nitric oxide to form S-nitrosocysteine in proteins can occur through various mechanisms including reaction of the nitric oxide radical, formation of nitrogen trioxide, peroxynitrite formation followed by homolytic cleavage to form nitric oxide, and nitrous acid reaction in acidic regions.29-35 There is a suggestion that the oxidation of nitric oxide to form nitrogen trioxide is favored in a hydrophobic environment.31,35 The nitrosylation of proteins is thought to be mediated through the action of S-nitrosoglutathione through a process of transnitrosylation.6,36,37 Most protein S-nitrosothiols are thought to be reduced by intracellular thiols to yield the parent thiol38,39, although some protein Snitrosothiol derivatives have unusual stability.40 Paige and coworkers40 suggested that there is a conformational change in the target protein after S-nitrosylation. In support of this concept, Schreiter and coworkers41 used crystallography to show that S-nitrosylation caused a reversible conformational change in blackn tuna myoglobin.