Publication Date:
2014-12-17
Description:
Glutathionylation plays a central role in cellular redox regulation and anti-oxidative defense. Glutaredoxins are primarily responsible reversing glutathionylation and their activity therefore affects a range of cellular processes, making them prime candidates for computational systems biology studies. However, two distinct kinetic mechanisms involving either one (monothiol) or both (dithiol) active-site cysteines have been proposed for their deglutathionylation activity and initial studies predicted that computational models based on either of these mechanisms will have different structural and kinetic properties. Further, a number of other discrepancies including the relative activity of active-site mutants and contrasting reciprocal plot kinetics have also been reported for these redoxins. Using kinetic modeling, we show that the dithiol and monothiol mechanisms are identical and, we were also able to explain much of the discrepant data found within the literature on glutaredoxin activity and kinetics. Moreover, our results have revealed how an apparently futile side-reaction in the monothiol mechanism may play a significant role in regulating glutaredoxin activity in vivo.
Print ISSN:
0144-8463
Electronic ISSN:
1573-4935
Topics:
Biology
,
Chemistry and Pharmacology
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