title: 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 0.48 ± 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.
authors.affiliation: Department of Biotechnology, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Olena
authors.initials: O
authors.lastname: Dobrovolska
authors.forename: Elena
authors.initials: E
authors.lastname: Shumilina
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.forename: Alexander
authors.initials: A
authors.lastname: Dikiy
mesh_terms: D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D009097:Multienzyme Complexes; D009247:NADH, NADPH Oxidoreductases; C466433:thioredoxin glutathione reductase