Structural Analysis of Glutaredoxin Domain of Mus musculus Thioredoxin Glutathione Reductase
Abstract
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 0.4860.10 A°
. The
structure represents a sandwich-like molecule composed of a four stranded b-sheet flanked by five a–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.