Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling

Abstract

Although it is widely accepted that S-nitrosation occurs in vivo, questions remain regarding S-nitrosation as a signaling mechanism. The chemistry of S-nitrosation includes NO oxidation to N(2)O(3) followed by reaction with thiolates, radical recombination of NO and thiyl radicals, and transition metal catalyzed pathways. Once formed, nitrosothiols can be transferred between small molecule or protein thiols through transnitrosation reactions. The pathways that lead to selective S-nitrosation of only a subset of cellular cysteines remain largely unknown. Selectivity may be conferred through colocalization with NOS isoforms, protein-protein interaction driven transnitrosation reactions, regulation of S-nitrosoglutathione levels, or directed denitrosation of protein nitrosothiols.