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Nitrosylation, specifically S-nitrosylation, involves the covalent incorporation of a nitric oxide moiety into thiol groups, to form S-nitrosothiol (SNO). Where the thiol group belongs to a subset of specific cysteine residues in proteins, the resulting SNO is an S-nitrosoprotein. S-Nitrosylation is a form of post-translational protein modification with similarities to phosphorylation.[1] S-Nitrosylation meets the criteria for validation as a signaling mechanism in that it is stimulus evoked,[2] precisely targeted,[3] reversible,[4] spatiotemporally restricted[5][6] and necessary for specific cell responses.[7] The first protein whose activity was shown to be regulated by S-nitrosylation in this fashion was the NMDA-type glutamate receptor in the brain.[8][9] S-nitrosylation has since been shown to be ubiquitous in biology, having been demonstrated to occur in all phylogenetic Kingdoms[10][11] and has been described as the prototypic redox-based signalling mechanism,[12] hypothesised to have evolved on primordial Earth.[13]

Nitrosylation results in a molecule "R" adducted with the group N=O

The reverse process of S-nitrosylation is termed denitrosylation, which in addition to occurring spontaneously in the presence of metal ions and under conditions of photolysis,[14] has recently been demonstrated to be an enzymically controlled process. S-Nitrosoglutathione reductase (GSNOR), which accelerates the decomposition of S-nitrosoglutathione (GSNO) and other SNO-proteins, is an alcohol dehydrogenase class III isoenzyme which has been shown to be conserved from bacteria to humans.[15] Similarly, the thioredoxin/thioredoxin reductase system catalyzes the denitrosylation of a number of S-nitrosoproteins[16][17][18] Aberrant or dysregulated denitrosylation or S-nitrosylation has been associated with stroke (cerebral ischemia)[19] and a number of chronic degenerative diseases, including Parkinson's and Alzheimer's disease[20][21][22][23] and Amyotrophic Lateral Sclerosis (ALS).[24] There is an emerging role of S-nitrosylation in cancer biology.[25] S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer [26]


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