Thioredoxin reductase 1 (TXNRD1) (TXNRD1)

Thioredoxin reductase 1 (TXNRD1) is a cytosolic NADPH-dependent flavoenzyme essential for maintaining cellular redox homeostasis by reducing thioredoxin (Trx) (UniProt P30041). It is a member of the selenoprotein family, characterized by a highly reactive selenocysteine (Sec) residue within its C-terminal catalytic site (-Gly-Cys-Sec-Gly-), which is indispensable for its electron transfer function (Becker et al., 2000, Eur. J. Biochem.). This enzyme system supports critical biological processes, including DNA synthesis via ribonucleotide reductase, antioxidant defense, and the regulation of redox-sensitive transcription factors. Due to its role in promoting cell survival and proliferation, TXNRD1 is frequently overexpressed in various cancers to counteract elevated oxidative stress (Zhang et al., 2017, Free Radic. Biol. Med.). Consequently, the catalytic site of TXNRD1 is a major therapeutic target; inhibitors like auranofin covalently bind to the selenocysteine residue, effectively blocking enzyme activity (PubChem CID 24199). This inhibition triggers a cascade of reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and ultimately, programmed cell death in cancer cells.

Other names

Thioredoxin reductase catalytic site within the selenoproteinTrxR1Thioredoxin reductaseTR1TRXR1Selenoprotein TR

Inhibition of the enzyme's catalytic activity, primarily through covalent binding or coordination to the selenocysteine residue in the C-terminal active site, leading to increased oxidative stress and apoptosis.