Disease relevance of ECs3448

• Two thioredoxins have been described in Escherichia coli, TrxA and Trx2 [1].
• The N-terminal domain of PILB from Neisseria meningitidis is a disulfide reductase that can recycle methionine sulfoxide reductases [2].
• Thioredoxin from the cyanobacterium Anabaena 7119 serves as electron donor to ribonucleotide reductase and as a protein disulfide reductase [3].
• Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein disulfide reductase [4].

High impact information on ECs3448

• Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat expansion [5].
• These results, which show that the N-terminal domain exhibits a disulfide reductase activity and probably has a thioredoxin-fold, are discussed in relation to its possible functional role in Neisseria [2].
• Moreover, the gene coding for Trx2 is under control of the oxidative stress transcription factor OxyR in E. coli [1].
• Trx1, Trx2, and Grx1 levels increased after exposure to hydrogen peroxide and decreased after exposure to mercaptoethanol [6].
• The enzymatic activity of Trx2 as a protein-disulfide reductase is increased by preincubation with dithiothreitol, suggesting that oxidation of cysteine residues other than the ones in the active site might regulate its activity [7].

Chemical compound and disease context of ECs3448

• Identification of a coenzyme A--glutathione disulfide (DSI), a modified coenzyme A disulfide (DSII), and a NADPH-dependent coenzyme A--glutathione disulfide reductase in E. coli [8].

Biological context of ECs3448

• Trx2 contains two distinct domains: an N-terminal domain of 32 amino acids including two CXXC motifs and a C-terminal domain, with the conserved active site, Trp-Cys-Gly-Pro-Cys, showing high homology to the prokaryotic thioredoxins [7].
• This suggests that Trx2 may play a role in the cellular defense against oxidative stress [1].
• Thus when E. coli TrxA is combined in a recombinant fusion protein with P. haemolytica A1 Gcp, productive folding of the glycoprotease can occur as a result of the chaperone action of the protein disulfide reductase coupled with its ability to retain the fusion gene product in the E. coli cytoplasm [9].

Anatomical context of ECs3448

• Mutations of the membrane-bound disulfide reductase DsbD that block electron transfer steps from cytoplasm to periplasm in Escherichia coli [10].

Associations of ECs3448 with chemical compounds

• A truncated form of the protein, lacking the N-terminal domain, is insensitive to the presence of dithiothreitol, further confirming the involvement of the additional cysteine residues in modulating Trx2 activity [7].
• Thus, under aerobic conditions selenite catalyzed, NADPH-dependent redox cycling with oxygen, a large oxygen-dependent consumption of NADPH and oxidation of reduced thioredoxin inhibiting its disulfide-reductase activity [11].

Other interactions of ECs3448

• Many bacteria also express a flavoprotein, AhpF, which acts as a dedicated disulfide reductase to recycle the bacterial peroxiredoxin, AhpC, during catalysis [12].

Analytical, diagnostic and therapeutic context of ECs3448

• Finally, Trx2 is present normally in growing E. coli cells as shown by Western blot analysis [7].

References