Structural highlights
Function
[TRXR3_MOUSE] Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun QA, Kirnarsky L, Sherman S, Gladyshev VN. Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3673-8. Epub 2001 Mar 20. PMID:11259642 doi:10.1073/pnas.051454398
- ↑ Su D, Novoselov SV, Sun QA, Moustafa ME, Zhou Y, Oko R, Hatfield DL, Gladyshev VN. Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation. J Biol Chem. 2005 Jul 15;280(28):26491-8. Epub 2005 May 18. PMID:15901730 doi:M503638200
- ↑ Dobrovolska O, Shumilina E, Gladyshev VN, Dikiy A. 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. PMID:23300818 doi:10.1371/journal.pone.0052914
