Selenoprotein

Selenoproteins are a specialized group of proteins that contain the 21st amino acid, selenocysteine, which is incorporated into the polypeptide chain in response to a recoded UGA stop codon. The human selenoproteome consists of 25 proteins, including glutathione peroxidases (GPXs), thioredoxin reductases (TXNRDs), and iodothyronine deiodinases (DIOs), most of which function as oxidoreductases (Labunskyy et al., 2014). These enzymes play critical roles in maintaining cellular redox balance, protecting against oxidative damage, and regulating thyroid hormone activation and inactivation. Dysregulation of selenoprotein expression or selenium deficiency is associated with various pathologies, including increased cancer risk, impaired immune function, and cardiovascular disorders like Keshan disease (Rayman, 2012). In drug development, selenoproteins are targeted either through nutritional supplementation to restore enzyme activity or through specific inhibitors like auranofin, which targets thioredoxin reductase for the treatment of rheumatoid arthritis and potentially cancer. Because selenium has a very narrow therapeutic index, pharmacological interventions must be carefully monitored to avoid selenosis and other metabolic complications (StatPearls).

Other names

Selenium-dependent enzymesSelenoproteomeSelenoenzymesSelenium-containing proteins

Selenium supplementation provides the essential trace element for the co-translational synthesis of selenocysteine, which is incorporated into the active site of selenoproteins to maintain enzymatic activity (NIH Office of Dietary Supplements). Ebselen acts as a small-molecule mimic of glutathione peroxidase, catalyzing the reduction of reactive oxygen species (PubMed: 25611108). Auranofin acts as an irreversible inhibitor of thioredoxin reductase by binding to the selenocysteine residue in the enzyme's C-terminal active site (PubMed: 30635131).