The glutaredoxin mono- and di-thiol mechanisms for deglutathionylation are functionally equivalent : implications for redox systems biology
Date
2015
Journal Title
Journal ISSN
Volume Title
Publisher
Portland Press
Abstract
Glutathionylation plays a central role in cellular redox regulation and anti-oxidative defence. Grx (Glutaredoxins) are
primarily responsible for 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
modelling, 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 Grx 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 Grx activity
in vivo.
Description
CITATION: Mashamaite, L. N., Rohwer, J. M. & Pillay, C. S. 2015. The glutaredoxin mono- and di-thiol mechanisms for deglutathionylation are functionally equivalent : implications for redox systems biology. Bioscience Reports, 35, e00173, doi:10.1042/BSR20140157.
The original publication is available at http://www.bioscirep.org
The original publication is available at http://www.bioscirep.org
Keywords
Kinetics, Redox regulation, Glutaredoxin, Thiol
Citation
Mashamaite, L. N., Rohwer, J. M. & Pillay, C. S. 2015. The glutaredoxin mono- and di-thiol mechanisms for deglutathionylation are functionally equivalent : implications for redox systems biology. Bioscience Reports, 35, e00173, doi:10.1042/BSR20140157.