ABSTRACT
Accumulating data suggests that nitric oxide (NO) regulates a diverse array of biological processes via nitrosylation/denitrosylation of proteins (1). Nitrosylation is the binding of a NO group and denitrosylation is the removal of a NO group from a protein or peptide. Proteins have two main nitrosylation targets: reactive metal centers (metal-nitrosylation) and cysteine residues (S-nitrosylation). Nitrosylation of critical cysteines or metals regulates protein function. In addition, nitrosylation is specifically targeted and rapidly reversible, allowing cells to dynamically modify signaling in response to physiologic stimuli; however, unlike more traditional posttranslational modifications, such as phosphorylation, nitrosylation of proteins is, at least in part, non-enzymatically mediated. Instead, complex and incompletely understood intracellular redox chemistry results in the addition or deletion of NO groups from proteins. Thus, nitrosylation directly
translates shifts in the cellular redox environment to changes in protein function. Although the activity of many proteins is modified by nitrosylation in cell free systems, it has been much more difficult to identify proteins that are endogenously nitrosylated in cells. Identification of endogenously nitrosylated proteins is technically challenging because the intracellular levels of nitrosylated proteins are at the limits of detection of currently available assays; however, strong evidence indicates that several cell-signaling pathways are regulated by endogenous nitrosylation. This chapter discusses how specificity and reversibility of nitrosylation reactions are achieved and reviews some of the signaling pathways that are regulated by nitrosylation/denitrosylation intracellularly.
