title: How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?
abstract: Over the last 25 years protein S-nitrosylation, also known more correctly as S-nitrosation, has been progressively implicated in virtually every nitric oxide-regulated process within the cardiovascular system. The current, widely-held paradigm is that S-nitrosylation plays an equivalent role as phosphorylation, providing a stable and controllable post-translational modification that directly regulates end-effector target proteins to elicit biological responses. However, this concept largely ignores the intrinsic instability of the nitrosothiol bond, which rapidly reacts with typically abundant thiol-containing molecules to generate more stable disulfide bonds. These protein disulfides, formed via a nitrosothiol intermediate redox state, are rationally anticipated to be the predominant end-effector modification that mediates functional alterations when cells encounter nitrosative stimuli. In this review we present evidence and explain our reasoning for arriving at this conclusion that may be controversial to some researchers in the field.
authors.affiliation: King's College London, Cardiovascular Division, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Wolhuter
authors.affiliation: King's College London, Cardiovascular Division, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. Electronic address: philip.eaton@kcl.ac.uk.
authors.forename: Philip
authors.initials: P
authors.lastname: Eaton
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D015538:Nitrosation; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D026403:S-Nitrosothiols / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D004220:Disulfides; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D013879:Thioredoxins; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000445:Aldehyde Oxidoreductases; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C087006:formaldehyde dehydrogenase, glutathione-independent; D013880:Thioredoxin-Disulfide Reductase
keywords: Cysteine; Nitric oxide; Redox; S-nitrosation; S-nitrosylation; Thiol