| Description |
Protein S-glutathionylation has been shown, to regulate a variety of cellular processes by modulating protein function, and, to prevent irreversible oxidation of protein thiols. The enzymes of the glycolytic pathway are usually down-regulated by S-glutathionylation and they also constitute important targets for dual regulation by Glutaredoxin and Thioredoxin. Triose-phosphate isomerase (TIM), a ubiquitous glycolytic enzyme that catalyzes the interconversion between glyceraldehyde 3-phosphate and dihydroxy-acetone phosphate has been shown to be a target of S-glutathionylation. In our study we have demonstrated that S-glutathionylation of 2 specific cysteines (Cys13 & Cys217) results in inhibition of TIM by using mass spectrometric analysis, biochemical assays and computer simulations. Further we have explored the structural interaction between the glycolytic enzyme TIM from the malarial parasite and the redox protein thioredoxin (Trx) using NMR spectroscopy. The structure of the TIM-Trx complex seems to provide a physical basis for explaining the deglutathionylating activity of Trx on TIM.
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