title: Redox active thiol sensors of oxidative and nitrosative stress.
abstract: CONCLUSIONS
  The reactivity of the thiol in the side chain of cysteines is exploited by bacterial regulatory proteins that sense and respond to reactive oxygen and nitrogen species.
  
  
  BACKGROUND
  Charged residues and helix dipoles diminish the pKa of redox active cysteines, resulting in a thiolate that is stabilized by neighboring polar amino acids. The reaction of peroxides with thiolates generates a sulfenic acid (-SOH) intermediate that often gives rise to a reversible disulfide bond. Peroxide-induced intramolecular and intermolecular disulfides and intermolecular mixed disulfides modulate the signaling activity of members of the LysR/OxyR, MarR/OhrR, and RsrA family of transcriptional regulators. Thiol-dependent regulators also help bacteria resist the nitrosative and nitroxidative stress. -SOHs, mixed disulfides, and S-nitrosothiols are some of the post-translational modifications induced by nitrogen oxides in the thiol groups of OxyR and SsrB bacterial regulatory proteins. Sulfenylation, disulfide bond formation, S-thiolation, and S-nitrosylation are reversible modifications amenable to feedback regulation by antioxidant and antinitrosative repair systems. The structural and functional changes engaged in the thiol-dependent sensing of reactive species have been adopted by several regulators to foster bacterial virulence during exposure to products of NADPH phagocyte oxidase and inducible nitric oxide synthase.
  
  
  RESULTS
  Investigations with LysR/OxyR, MarR/OhrR, and RsrA family members have helped in an understanding of the mechanisms by which thiols in regulatory proteins react with reactive species, thereby activating antioxidant and antinitrosative gene expression.
  
  
  CONCLUSIONS
  To define the determinants that provide selectivity of redox active thiolates for some reactive species but not others is an important challenge for future investigations.
authors.affiliation: Department of Microbiology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA. andres.vasquz-torres@ucdenver.edu
authors.forename: Andrés
authors.initials: A
authors.lastname: Vázquez-Torres
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds