Structural analysis of glutaredoxin domain of Mus musculus thioredoxin glutathione reductase

PLoS One. 2012;7(12):e52914. doi: 10.1371/journal.pone.0052914. Epub 2012 Dec 26.


Thioredoxin glutathione reductase (TGR) is a member of the mammalian thioredoxin reductase family that has a monothiol glutaredoxin (Grx) domain attached to the thioredoxin reductase module. Here, we report a structure of the Grx domain of mouse TGR, determined through high resolution NMR spectroscopy to the final backbone RMSD value of 0.48 ± 0.10 Å. The structure represents a sandwich-like molecule composed of a four stranded β-sheet flanked by five α-helixes, with the CxxS active motif located on the catalytic loop. We structurally characterized the glutathione-binding site in the protein and describe sequence and structural relationships of the domain with glutaredoxins. The structure illuminates a key functional center that evolved in mammalian TGRs to act in thiol-disulfide reactions. Our study allows us to hypothesize that Cys105 might be functionally relevant for TGR catalysis. In addition, the data suggest that the N-terminus of Grx acts as a possible regulatory signal also protecting the protein active site from unwanted interactions in cellular cytosol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / metabolism
  • NADH, NADPH Oxidoreductases / chemistry*
  • NADH, NADPH Oxidoreductases / metabolism
  • Protein Conformation


  • Multienzyme Complexes
  • NADH, NADPH Oxidoreductases
  • thioredoxin glutathione reductase