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Target intelligence / Profile preview
Thiol-disulfide oxidoreductase system (TDOR)
- Target
- TDOR
- Molecular classification
- Enzyme, Thioredoxin superfamily member, Oxidoreductase
01
Overview
The thiol-disulfide oxidoreductase system comprises enzymes that catalyze the formation, isomerization, and reduction of disulfide bonds in proteins, ensuring their correct folding and maintaining redox balance within cells. Members of this system—including protein disulfide isomerase, thioredoxin, and the Dsb family—generally possess a thioredoxin fold and a CXXC active-site motif, enabling them to transfer disulfide bonds between proteins via thiol-disulfide exchange reactions. Their activity is essential for cell viability, proper protein secretion, and protection against cellular stress, and dysfunction of these enzymes is implicated in several diseases, such as diabetes and infection.
- Other names
- thiol-disulfide oxidoreductaseTDORprotein disulfide isomerase (PDI)Dsb proteins (in bacteria)thioredoxin (TrxA, a core member)
02
Mechanism of action
Redox modulation (altering the oxidative/reductive balance within target proteins); Inhibition or activation of disulfide bond formation; Inhibition of protein-folding machinery; Disruption of redox-dependent signalling pathways
03
Biological functions
Oxidative protein foldingRedox regulationDisulfide bond formationDisulfide bond isomerizationDisulfide bond reductionER-associated degradation of proteinsRegulation of ER stress response and calcium homeostasis
04
Disease associations
Diabetes (impairment of ER-localized TDORs can cause disease)Protein misfolding disordersInfection (bacterial TDORs are essential for virulence)Other (broad implications in disease due to impact on protein folding; e.g., neurodegenerative disease)
05
Safety considerations
Modulation may impair protein folding, leading to accumulation of misfolded proteins and cellular toxicityPotential for adverse effects due to disruption of redox homeostasis and essential cellular processes
06
Interacting drugs
No fully validated drugs specifically targeting the whole system, but inhibitors of individual components such as thioredoxin reductase exist (e.g., auranofin for TrxR)
07
Biomarkers
Levels of protein disulfide isomerase (PDI) and thioredoxin are used as biomarkers in several pathological conditions, especially those involving ER stress and oxidative damage
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