Which Mutations Make Glutaredoxins Redox-Active?

  • Author: ChemistryViews.org
  • Published: 25 April 2020
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
  • Source / Publisher: Nature Communications/Springer Nature Limited
thumbnail image: Which Mutations Make Glutaredoxins Redox-Active?

Glutaredoxins (example pictured) are small proteins. Class I glutaredoxins are enzymatically active in redox reactions, for example, in the synthesis of DNA precursors. The substrate of these enzymatically active glutaredoxins is glutathione. There are also class II glutaredoxins, which are enzymatically inactive proteins that can bind iron-sulfur clusters. These proteins are important in the metabolism of iron. Which structural differences are responsible for these different functions had not been fully understood so far.

Holger Gohlke, University of Düsseldorf, Germany, and Forschungszentrum Jülich GmbH, Germany, Bruce Morgan, Saarland University, Saarbrücken, Germany, Marcel Deponte, University of Kaiserslautern, Germany, and colleagues have investigated these structural differences. The team used the yeast glutaredoxin ScGrx7 as a model system and introduced mutations to study the effects of the resulting structural changes.

NMR spectroscopic measurements had shown that at least four protein areas differ between enzymatically active and inactive glutaredoxins. The team identified and characterized key residues from these areas and quantified their contribution to the enzymatic activity by systematically modifying the proteins via genetic mutations. They studied the resulting proteins using enzymatic assays and molecular dynamics (MD) simulations.

The researchers found that all four known protein areas that have structural differences directly or indirectly affect the activity. A loop in the protein structure caused a particularly important difference: It is longer in enzymatically inactive glutaredoxins. When the researchers artificially shortened it, activity increased slightly. Further targeted mutations allowed the team to convert an inactive class II glutaredoxin to an active enzyme. Overall, the work provides an improved understanding of the mechanism of glutaredoxin catalysis.



Article Views: 911

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter

Magazine of Chemistry Europe (16 European Chemical Societies)published by Wiley-VCH