Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A thiol-specific antioxidant enzyme (TSA), which provides protection against the inactivation of other enzymes by the thiol/Fe(III)/oxygen system, was previously isolated and cloned. We investigated the mechanism by which TSA protects biomolecules from oxidative damage caused by the thiol-containing oxidation system using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Thiyl radicals from dithiothreitol (.DTT) were produced by horseradish peroxidase/H2O2 under aerobic and anaerobic conditions and by the Fe(III)/oxygen system. The formation of DMPO-.DTT radical adducts were inhibited by TSA regardless of the thiyl radical-generating conditions used. The active mutant C170S also quenched the signals of the radical adduct, whereas the inactive mutant C47S did not exert any effect. It was also found that C170S has a higher rate at the initial stage of the reaction than that of the native enzyme, although C170S failed to remove DMPO-.DTT radical adducts completely. These results indicate that only active TSA can catalyze the removal of thiyl radicals, and cysteine 47 is required for this activity. In addition, thiyl radicals react with oxygen to generate unidentified thiylperoxy species. Fe.EDTA reacts with this species to generate a reactive radical that can abstract hydrogen atom from ethanol to produce a hydroxyethyl radical. This reactive thiyl-oxygen radical is believed to be responsible for causing deleterious effects on biomolecules. Together, our data indicate that TSA protects biomolecules from oxidative damage by catalyzing the removal of thiyl radicals before they generate more reactive radicals. However, presently we cannot rule out the possibility that TSA can also use other thiol-containing species as substrates.
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PMID:On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. 829 8

Mycobacterium tuberculosis (H37Rv), the causative agent of the dreaded disease tuberculosis, contains three thioredoxins and a single thioredoxin reductase. Thioredoxin reductase is a member of the pyridine-nucleotide disulfide oxidoreductase family of flavoenzymes. The thioredoxin reductase gene with a His tag at the C-terminus was expressed in Escherichia coli and purified. The dimeric (70 kDa) protein was incubated with 10 mM DTT for 30 min and then crystallized using the hanging-drop vapour-diffusion method in the presence of 15% PEG 3350 and phosphate-citrate buffer pH 5 at room temperature (298 K). A diffraction data set complete to 3 A resolution has been collected under cryoconditions and the space group was determined to be P4(1)2(1)2, with unit-cell parameters a = 107.4, c = 118.2 A. Matthews coefficient calculations revealed the presence of two monomers in the asymmetric unit.
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PMID:Expression, purification, crystallization and preliminary X-ray crystallographic studies of Mycobacterium tuberculosis thioredoxin reductase. 1503 84

DREAM/KChIP3 (Downstream Regulatory Element Antagonist Modulator) is a multifunctional Ca(2+)-binding protein that acts in the nucleus as a Ca(2+)-dependent transcriptional repressor. Binding to DNA and repressor activity of DREAM is regulated by Ca(2+), specific post-translational modifications as well as by protein-protein interactions with several nucleoproteins. Here, using the yeast two-hybrid assay, we characterized the interaction of DREAM with peroxiredoxin 3 (Prdx3), an antioxidant enzyme that uses the thioredoxin system as electron donor. Importantly, the DREAM/Prdx3 interaction is Ca(2+) dependent and is blocked by DTT. Coexpression of Prdx3 enhances DREAM binding to DRE sites and its repressor activity in vivo. Two cysteine residues in the N-terminal domain of DREAM are responsible for the redox modulation of its activity. Double Cys to Ser substitution results in a mutant DREAM with stronger repressor activity. Finally, we show that transient DREAM knockdown sensitizes PC12 cells to H(2)O(2)-induced oxidative stress, suggesting a protective role for DREAM against oxidative damage.
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PMID:Redox signaling regulates transcriptional activity of the Ca2+-dependent repressor DREAM. 2061 65