Dobrovolska, OlenaShumilina, ElenaGladyshev, VadimDikiy, Alexander2013-10-182012Dobrovolska, Olena, Elena Shumilina, Vadim N. Gladyshev, and Alexander Dikiy. 2012. Structural analysis of glutaredoxin domain of mus musculus thioredoxin glutathione reductase. PLoS ONE 7(12): e52914.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181099Thioredoxin 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.en-USBiologyBiochemistryProteinsProtein StructureEnzymesBiophysicsComputational BiologyMacromolecular Structure AnalysisSequence AnalysisProteomicsSpectrometric Identification of ProteinsJournal Article2013-10-1810.1371/journal.pone.0052914