Thiol- and selenol-containing proteins

Thiol- and selenol-containing proteins are a broad class of redox-active molecules characterized by the presence of highly nucleophilic cysteine (thiol) or selenocysteine (selenol) residues [1.2.1, 1.2.2]. These proteins, which include essential enzymes such as thioredoxin reductase (TrxR) and glutathione peroxidase (GPx), are fundamental to cellular redox homeostasis, antioxidant defense, and the regulation of apoptosis [1.1.1, 1.3.3]. Due to the exceptional affinity of soft metals (e.g., gold, mercury) and electrophiles for sulfur and selenium atoms, these proteins serve as primary targets for gold-based anticancer drugs like auranofin and are also the main sites of toxicity for environmental contaminants like methylmercury [1.2.3, 1.3.2]. In many cancers, these proteins are overexpressed to mitigate high levels of reactive oxygen species, making them attractive targets for inducing oxidative stress-mediated cell death [1.1.1, 1.3.4]. However, the ubiquitous nature of thiol groups in the proteome poses significant challenges for achieving target specificity and avoiding systemic toxicity [1.2.3, 1.4.2]. Beyond cancer, these proteins are involved in the pathophysiology of neurodegenerative diseases and infections, where their redox-regulating capacity is often compromised [1.2.1, 1.3.2]. Therapeutic strategies often focus on the selective inhibition of specific members like TrxR1, though many current agents exhibit polypharmacology across the entire class [1.3.2, 1.3.4].

Other names

Cysteine- and selenocysteine-containing proteinsRedox-active proteinsSulfhydryl- and selenohydryl-containing proteinsThioredoxin system proteinsSelenoproteins

Covalent inhibition of enzyme activity through binding to nucleophilic thiol or selenol groups, leading to oxidative stress and apoptosis [1.1.1, 1.3.2].