Nitric oxide and Posttranslational modification of the vascular proteome - S-nitrosation of reactive thiols

Nitric oxide ( NO center dot) is known to exert its effects via guanylyl cyclase and cyclic GMP-dependent pathways and by cyclic GMP-independent pathways, including the posttranslational modification of proteins. Much ongoing research is focused on defining the mechanisms of NO center dot-mediated protein modification, the identity and function of the modified proteins, and the significance of these changes in health and disease. S-nitrosation or thionitrite formation has only been found on a limited number of residues in a subset of proteins in in vitro and in vivo studies. Protein S-nitrosation also appears to be reversible. There are several theories about the in vivo S-nitrosating agent, and most suggest a role for oxidation products of NO center dot in this process. Flux in cellular S-nitrosoprotein pools appears to be regulated by NO center dot availability and is redox-sensitive. An analysis of S-nitrosation in candidate proteins has clarified the mechanism by which NO center dot regulates enzymatic and cellular functions. These findings suggest the utility of using proteomic methods to identify unique targets for protein S-nitrosation to understand further the molecular mechanisms of the effects of NO center dot.