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| | <StructureSection load='3qfb' size='340' side='right'caption='[[3qfb]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='3qfb' size='340' side='right'caption='[[3qfb]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qfb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qfb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qfa|3qfa]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRIM12, KDRF, TXNRD1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TRDX, TRX, TRX1, TXN ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thioredoxin-disulfide_reductase Thioredoxin-disulfide reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.9 1.8.1.9] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfb OCA], [https://pdbe.org/3qfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfb RCSB], [https://www.ebi.ac.uk/pdbsum/3qfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfb ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfb OCA], [https://pdbe.org/3qfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfb RCSB], [https://www.ebi.ac.uk/pdbsum/3qfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TRXR1_HUMAN TRXR1_HUMAN]] Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.<ref>PMID:9774665</ref> <ref>PMID:8577704</ref> <ref>PMID:15199063</ref> <ref>PMID:18042542</ref> [[https://www.uniprot.org/uniprot/THIO_HUMAN THIO_HUMAN]] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref> ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref>
| + | [https://www.uniprot.org/uniprot/TRXR1_HUMAN TRXR1_HUMAN] Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.<ref>PMID:9774665</ref> <ref>PMID:8577704</ref> <ref>PMID:15199063</ref> <ref>PMID:18042542</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thioredoxin-disulfide reductase]]
| + | [[Category: Becker K]] |
| - | [[Category: Becker, K]] | + | [[Category: Fritz-Wolf K]] |
| - | [[Category: Fritz-Wolf, K]] | + | [[Category: Kehr S]] |
| - | [[Category: Kehr, S]] | + | [[Category: Rahlfs S]] |
| - | [[Category: Rahlfs, S]] | + | [[Category: Stumpf M]] |
| - | [[Category: Stumpf, M]] | + | |
| - | [[Category: Electron transport]]
| + | |
| - | [[Category: Homodimeric pyridine nucleotide disulfide oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Protein-protein complex]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Thioredoxin fold]]
| + | |
| Structural highlights
Function
TRXR1_HUMAN Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.[1] [2] [3] [4]
Publication Abstract from PubMed
Thioredoxin reductase 1 (TrxR1) is a homodimeric flavoprotein crucially involved in the regulation of cellular redox homeostasis, growth, and differentiation. Its importance in various diseases makes TrxR1 a highly interesting drug target. Here we present the first crystal structures of human TrxR1 in complex with its substrate thioredoxin (Trx). The carboxy-terminal redox centre is found about 20 A apart from the amino-terminal redox centre, with no major conformational changes in TrxR or Trx. Thus, our structure confirms that the enzyme uses a flexible C-terminal arm for electron transport to its substrates, which is stabilized by a guiding bar for controlled transfer. This notion is supported by mutational analyses. Furthermore, essential residues of the interface region were characterized both structurally and functionally. The structure provides templates for future drug design, and contributes to our understanding of redox regulatory processes in mammals.
Crystal structure of the human thioredoxin reductase-thioredoxin complex.,Fritz-Wolf K, Kehr S, Stumpf M, Rahlfs S, Becker K Nat Commun. 2011 Jul 12;2:383. doi: 10.1038/ncomms1382. PMID:21750537[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hofmann ER, Boyanapalli M, Lindner DJ, Weihua X, Hassel BA, Jagus R, Gutierrez PL, Kalvakolanu DV. Thioredoxin reductase mediates cell death effects of the combination of beta interferon and retinoic acid. Mol Cell Biol. 1998 Nov;18(11):6493-504. PMID:9774665
- ↑ Tamura T, Stadtman TC. A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1006-11. PMID:8577704
- ↑ Damdimopoulos AE, Miranda-Vizuete A, Treuter E, Gustafsson JA, Spyrou G. An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling. J Biol Chem. 2004 Sep 10;279(37):38721-9. Epub 2004 Jun 14. PMID:15199063 doi:http://dx.doi.org/10.1074/jbc.M402753200
- ↑ Dammeyer P, Damdimopoulos AE, Nordman T, Jimenez A, Miranda-Vizuete A, Arner ES. Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin reductase 1. J Biol Chem. 2008 Feb 1;283(5):2814-21. Epub 2007 Nov 27. PMID:18042542 doi:http://dx.doi.org/10.1074/jbc.M708939200
- ↑ Fritz-Wolf K, Kehr S, Stumpf M, Rahlfs S, Becker K. Crystal structure of the human thioredoxin reductase-thioredoxin complex. Nat Commun. 2011 Jul 12;2:383. doi: 10.1038/ncomms1382. PMID:21750537 doi:10.1038/ncomms1382
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