title: Selenocysteine in thiol/disulfide-like exchange reactions.
abstract: CONCLUSIONS
  Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity.
  
  
  BACKGROUND
  The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs.
  
  
  RESULTS
  We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions.
  
  
  CONCLUSIONS
  It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec.
authors.affiliation: Given Laboratory, Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA. Robert.Hondal@uvm.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hondal
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Marino
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D002384:Catalysis; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D054477:Glutaredoxins / Q000737:chemistry / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D012643:Selenium / Q000737:chemistry / Q000378:metabolism; D017279:Selenocysteine / Q000737:chemistry* / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D004220:Disulfides; D054477:Glutaredoxins; D013438:Sulfhydryl Compounds; D017279:Selenocysteine; D013455:Sulfur; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D012643:Selenium