S-nitrosylation is emerging as a specific and fundamental posttranslational protein modification: head-to-head comparison with O-phosphorylation.
Nitric oxide (NO) is a free-radical product of mammalian cell metabolism that plays diverse and important roles in the regulation of cell function. Biological actions of NO arise as a direct consequence of chemical reactions between NO or NO-derived species and protein targets. Reactions of NO with transition metals in target proteins have garnered the most attention to date as the principal mechanism of NO signaling; nonetheless, S-nitrosylation of protein Cys residues is rapidly moving to center stage in importance. In general, however, there has been a delay in adequate appreciation of the role of S-nitrosylation in biological signaling by NO. This lag is attributed to a poor understanding of the basis for selective targeting of NO to particular thiols, and methodological limitations in accurately quantifying this modification--recent breakthroughs in concepts and methods diminish these barriers. Here, we consider the wheres and whys of protein S-nitrosylation and its basis for specificity. Protein S-nitrosylation potentially represents a ubiquitous and fundamental mechanism for posttranslational control of protein activity on a par with that of O-phosphorylation.
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Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, Room LC-218, New York, NY 10021, USA. ssgross@med.cornell.edu
Hao
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Gross
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D000818:Animals; D001124:Argininosuccinate Synthase / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism; D019921:Biotinylation / Q000379:methods; D003545:Cysteine / Q000032:analysis / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
D009569:Nitric Oxide; D001710:Biotin; D001124:Argininosuccinate Synthase; D003545:Cysteine