Cellular thiol- and selenol-containing enzymes and proteins

Cellular thiol- and selenol-containing enzymes and proteins are a broad class of molecules essential for maintaining the redox balance within cells. This group includes key enzymes such as thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and various glutathione S-transferases, which utilize the high nucleophilicity of cysteine (thiol) and selenocysteine (selenol) residues to catalyze antioxidant reactions (PMID: 24913244, PMID: 30243833). These proteins are frequently overexpressed in cancer cells to mitigate the high levels of reactive oxygen species (ROS) generated by rapid metabolism, providing a survival advantage and resistance to chemotherapy (PMID: 29414301, PMID: 22503473). Therapeutic strategies often involve the use of electrophilic compounds or metal-based drugs that covalently bind to these nucleophilic sites, thereby inhibiting enzyme activity and triggering oxidative stress-induced apoptosis (PMID: 32350479). For example, the gold-containing drug auranofin is a potent inhibitor of thioredoxin reductase and has been investigated for its anti-cancer and anti-inflammatory properties (PMID: 29414301). Despite their therapeutic potential, the ubiquity of thiol and selenol groups across the human proteome poses significant challenges for drug selectivity, often leading to off-target effects and systemic toxicity (PMID: 30243833).

Other names

Thiol-containing proteinsSelenoproteinsRedox-active enzymesCysteine- and selenocysteine-containing proteins

Covalent inhibition of redox-active enzymes through binding to nucleophilic cysteine or selenocysteine residues, leading to the disruption of antioxidant systems and induction of oxidative stress (PMID: 29414301, PMID: 32350479).