2lv3

Publication Abstract from PubMed

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 A. The structure represents a sandwich-like molecule composed of a four stranded beta-sheet flanked by five alpha-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.

Structural analysis of glutaredoxin domain of Mus musculus thioredoxin glutathione reductase.,Dobrovolska O, Shumilina E, Gladyshev VN, Dikiy A PLoS One. 2012;7(12):e52914. doi: 10.1371/journal.pone.0052914. Epub 2012 Dec 26. PMID:23300818^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.