title: Specificity in S-nitrosylation: a short-range mechanism for NO signaling?
abstract: CONCLUSIONS
  Nitric oxide (NO) classical and less classical signaling mechanisms (through interaction with soluble guanylate cyclase and cytochrome c oxidase, respectively) operate through direct binding of NO to protein metal centers, and rely on diffusibility of the NO molecule. S-Nitrosylation, a covalent post-translational modification of protein cysteines, has emerged as a paradigm of nonclassical NO signaling.
  
  
  BACKGROUND
  Several nonenzymatic mechanisms for S-nitrosylation formation and destruction have been described. Enzymatic mechanisms for transnitrosylation and denitrosylation have been also studied as regulators of the modification of specific subsets of proteins. The advancement of modification-specific proteomic methodologies has allowed progress in the study of diverse S-nitrosoproteomes, raising clues and questions about the parameters for determining the protein specificity of the modification.
  
  
  RESULTS
  We propose that S-nitrosylation is mainly a short-range mechanism of NO signaling, exerted in a relatively limited range of action around the NO sources, and tightly related to the very controlled regulation of subcellular localization of nitric oxide synthases. We review the nonenzymatic and enzymatic mechanisms that support this concept, as well as physiological examples of mammalian systems that illustrate well the precise compartmentalization of S-nitrosylation.
  
  
  CONCLUSIONS
  Individual and proteomic studies of protein S-nitrosylation-based signaling should take into account the subcellular localization in order to gain further insight into the functional role of this modification in (patho)physiological settings.
authors.affiliation: 1 Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP) , Madrid, Spain .
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez-Ruiz
authors.forename: Inês M
authors.initials: IM
authors.lastname: Araújo
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo-Álvarez
authors.forename: Pablo
authors.initials: P
authors.lastname: Hernansanz-Agustín
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
authors.forename: Juan M
authors.initials: JM
authors.lastname: Serrador
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D021381:Protein Transport; D026403:S-Nitrosothiols / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D026403:S-Nitrosothiols; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III