The free radical ^·NO has important biological functions including vasorelaxation, blood clotting, neuronal plasticity, and cytotoxic activity {Moncada S et al. 1991;Kerwin JF Jr et al. 1995}. NO has been shown to interact with cysteine residues to form nitrosothiol adducts, thus altering the activity of proteins. Protein S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl group(s) of cysteine residue(s) of proteins, is a reversible post-translational protein modification, analogous to those created by phosphorylation or acetylation, involved in redox-based cellular signaling. The S-nitrosylation target proteins include hemoglobin {Gow AJ & Stamler JS. 1998}, serum albumin {Zhang YY et al. 1996;Stamler JS et al. 1992}, transcription factors {Nunoshiba T et al. 1993;Stamler JS et al. 1997;Hausladen A et al.1996;Berendji D et al. 1999}, G proteins {Lander HM et al. 1995}, ion channels {Xu L. et al. 1998}, and various enzymes {Rössig L et al. 1999;Bauer PM et al. 1999;Kröncke KD et al. 1997}.
S-nitrosylation possesses high spatial and temporal specificity on targeted cysteine residues {Hess DT et al. 2005;Hess DT et al. 2001}. In most cases, the specificity of S-nitrosylation is governed by the juxtaposed consensus acid-base motifs controlling targeted thiol pKa and nucleophilicity {Hess DT et al. 2001}. Since the hydrophobic environment facilitates the reaction for S-nitrosylation, the relative hy-drophobicity of the region surrounding the target thiol may provide a "hydrophobic motif" for protein S-nitrosylation {Hess DT et al. 2001}. In addition, the protein S-nitrosylation also depends on the colocalization of NO sources such as NOS with the targeted proteins and other nitrosylating equivalents {Hess DT et al. 2005;Hess DT et al. 2001;Derakhshan B et al. 2007;Iwakiri Y et al. 2006}. Once formed, the SNO moiety of an S-nitrosylated protein can be transferred to other thiols through a process termed transnitrosylation. Reducing glutathione (GSH) is the principal low molecular weight thiol that can be transnitrosylated, leading to the denitrosylation of those formed SNO proteins or vice-versa.

1. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43, 109-142. . (1991).

2. Kerwin JF Jr, Lancaster JR Jr, Feldman PL. Nitric oxide: a new paradigm for second messengers. J. Med. Chem. 38, 4343-4362. (1995).

3. Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature (London) 391, 169-173. (1998).

4. Zhang YY, Xu AM, Nomen M, Walsh M, Keaney JF Jr, Loscalzo J. Nitrosation of tryptophan residue(s) in serum albumin and model dipeptides. Biochemical characterization and bioactivity. J. Biol. Chem. 271, 14271-14279. (1996).

5. Stamler JS, Simon DI, Osborne JA, Mullins ME, Jaraki O, Michel T, Singel DJ, Loscalzo J. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. PNAS 89, 444-448. (1992)

6. Nunoshiba T, deRojas-Walker T, Wishnok JS, Tannenbaum SR, Demple B. Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. PNAS 90, 9993-9997. (1993)

7. Stamler JS, Toone EJ, Lipton SA, Sucher NJ. (S)NO signals: translocation, regulation, and a consensus motif. Neuron 18, 691-696. (1997)

8. Hausladen A, Privalle CT, Keng T, DeAngelo J, Stamler JS. Nitrosative stress: activation of the transcription factor OxyR. Cell 86, 719-729.(1996).

9. Berendji D, Kolb-Bachofen V, Zipfel PF, Skerka C, Carlberg C, Kröncke KD. Zinc finger transcription factors as molecular targets for nitric oxide-mediated immunosuppression: inhibition of IL-2 gene expression in murine lymphocytes. Mol. Med. 5, 721-730. (1999).

10. Lander HM, Ogiste JS, Pearce SF, Levi R, Novogrodsky A. Nitric oxide-stimulated guanine nucleotide exchange on p21ras. J. Biol. Chem. 270, 7017-7020. (1995).

11. Xu L, Eu JP, Meissner G, Stamler JS. Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279, 234-237. (1998).

12. Rössig L, Fichtlscherer B, Breitschopf K, Haendeler J, Zeiher AM, Mülsch A, Dimmeler S. Nitric oxide inhibits caspase-3 by S-nitrosation in vivo. J. Biol. Chem. 274, 6823-6826. (1999).

13. Bauer PM, Fukuto JM, Buga GM, Pegg AE, Ignarro LJ. Nitric oxide inhibits ornithine decarboxylase by S-nitrosylation. Biochem.Biophys. Res. Commun. 262, 355-358. (1999).

14. Kröncke KD, Fehsel K, Kolb-Bachofen V. Nitric oxide: cytotoxicity versus cytoprotection--how, why, when, and where? Nitric Oxide 1, 107-120. (1997).

15. Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS. Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol 6: 150-166.(2005)

16. Hess DT, Matsumoto A, Nudelman R, Stamler JS. S-nitrosylation: spectrum and specificity. Nat Cell Biol 3: E46-E49.(2001)

17. Derakhshan B, Hao G, Gross SS. Balancing reactivity against selectivity: The evolution of protein S-nitrosylation as an effec-tor of cell signaling by nitric oxide. Cardiovasc Res 75: 210-219.(2007).

18. Iwakiri Y, Satoh A, Chatterjee S, Toomre DK, Chalouni CM, Fulton D, Groszmann RJ, Shah VH, Sessa WC. Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. PNAS 103: 19777-19782.(2006).

Please send comments and suggestions to curator at: curator@ibibiosolutions.com.