Selenoprotein catalytic site (Sec-site)

Selenoprotein catalytic sites are specialized active centers within a unique class of proteins that incorporate the 21st amino acid, selenocysteine (Sec). These sites are characterized by the presence of a selenium atom, which provides significantly higher nucleophilicity and redox reactivity compared to the sulfur atom in cysteine (PMID: 24913744). This enhanced reactivity allows selenoproteins to efficiently catalyze essential biological processes, primarily involving redox signaling, antioxidant defense, and the regulation of thyroid hormones (PMID: 25130111). Key examples of proteins containing these sites include thioredoxin reductases (TrxR), glutathione peroxidases (GPx), and iodothyronine deiodinases (DIO) (PMID: 29414301). Because many cancer cells overexpress selenoproteins like TrxR1 to manage high levels of oxidative stress, these catalytic sites have emerged as critical therapeutic targets (PMID: 28235556). Drugs such as auranofin and various electrophilic small molecules exert their effects by covalently binding to the highly reactive Sec residue, thereby inhibiting the enzyme's function and inducing apoptosis in malignant cells (PMID: 29414301). However, the high reactivity of these sites also poses challenges for drug selectivity and potential systemic toxicity (PMID: 25130111).

Other names

Selenocysteine active siteSec-containing catalytic centerSelenoprotein redox centerSelenocysteine-mediated catalytic site

Covalent inhibition of the selenocysteine residue, competitive inhibition of redox activity, and induction of oxidative stress through enzyme inactivation.