S-nitrosylation signaling in cell biology.
S-Nitrosylated proteins form when a cysteine thiol reacts with nitric oxide (NO) in the presence of an electron acceptor to form an S-NO bond. Under physiological conditions, this posttranslational modification affects the function a wide array of cell proteins, ranging from ion channels to nuclear regulatory proteins. Recent evidence suggests that 1) S-nitrosylated proteins can be synthesized by exposure of specific redox-active motifs to NO, through transnitrosation/transfer reactions, or through metalloprotein-catalyzed reactions; 2) S-nitrosothiols can be sequestered in membranes, lipophilic protein folds, or in vesicles to preserve their activity; and 3) S-nitrosothiols can be degraded by a number of enzymes systems. These recent insights regarding the bioactivities, molecular signaling pathways, and metabolism of endogenous S-nitrosothiols have suggested several new therapies for disease ranging from cystic fibrosis to pulmonary hypertension.
Department of Pediatrics, Division of Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908 USA.
Benjamin M
BM
Gaston
Jeannean
J
Carver
Allan
A
Doctor
Lisa A
LA
Palmer
D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007555:Isoxazoles / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D026422:S-Nitrosoglutathione / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007555:Isoxazoles; D020030:Nitric Oxide Donors; D009687:Nuclear Proteins; D026403:S-Nitrosothiols; D014157:Transcription Factors; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase; C006303:acivicin