Nitric oxide and posttranslational modification of the vascular proteome: S-nitrosation of reactive thiols.
Nitric oxide (NO*) 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*-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* in this process. Flux in cellular S-nitrosoprotein pools appears to be regulated by NO* availability and is redox-sensitive. An analysis of S-nitrosation in candidate proteins has clarified the mechanism by which NO* 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*.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Diane E
DE
Handy
Joseph
J
Loscalzo
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D006801:Humans; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D009566:Nitrates; D020543:Proteome; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide