2zzc: Difference between revisions

Revision as of 14:03, 1 November 2023

Crystal structure of NADP(H):human thioredoxin reductase I

Structural highlights

2zzc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	FAD, NAP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Terpyridine-platinum(II) (TP-Pt(II)) complexes are known to possess DNA-intercalating activity and have been regarded as potential antitumor agents. However, their cytotoxic mechanism remains unclear. To investigate the possible mechanism, a series of TP-Pt(II) compounds were prepared and their biological activities assessed. The DNA binding activities of the aromatic thiolato[TP-Pt(II)] complexes were stronger than the aliphatic 2-hydroxylethanethiolato(2,2':6',2-terpyridine)platinum(II) [TP(HET)]. TP-Pt(II) complexes inhibited topoisomerase IIalpha or topoisomerase I activity at IC(50) values of about 5 microM and 10-20 microM, respectively, whereas the human thioredoxin reductase 1 (hTrxR1) activity was inhibited with IC(50) values in the range of 58-78 nM. At the cellular level, they possessed cytotoxicity with IC(50) values between 7 and 19 microM against HeLa cells. Additionally, using X-ray crystallography and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, we elucidated that the TP-Pt(II) complexes inhibited hTrxR1 activity by blocking its C-terminal active-site selenocysteine. Therefore, TP-Pt(II) complexes possess inhibitory activities against multiple biological targets, and they may be further studied as anticancer agents.

Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1.,Lo YC, Ko TP, Su WC, Su TL, Wang AH J Inorg Biochem. 2009 Jul;103(7):1082-92. Epub 2009 May 21. PMID:19525010^[5]

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

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:https://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:https://dx.doi.org/10.1074/jbc.M708939200
↑ Lo YC, Ko TP, Su WC, Su TL, Wang AH. Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1. J Inorg Biochem. 2009 Jul;103(7):1082-92. Epub 2009 May 21. PMID:19525010 doi:10.1016/j.jinorgbio.2009.05.006

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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:https://dx.doi.org/10.1074/jbc.M402753200

[4] 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:https://dx.doi.org/10.1074/jbc.M708939200

[5] Lo YC, Ko TP, Su WC, Su TL, Wang AH. Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1. J Inorg Biochem. 2009 Jul;103(7):1082-92. Epub 2009 May 21. PMID:19525010 doi:10.1016/j.jinorgbio.2009.05.006

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[5]

@@ Line 3: / Line 3: @@
 <StructureSection load='2zzc' size='340' side='right'caption='[[2zzc]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2zzc]] 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=2ZZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZZC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2zzc]] 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=2ZZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZZC 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=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 2.6&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zz0|2zz0]], [[2zzb|2zzb]]</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=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TXNRD1, KDRF ([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=2zzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zzc OCA], [https://pdbe.org/2zzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zzc RCSB], [https://www.ebi.ac.uk/pdbsum/2zzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zzc ProSAT]</span></td></tr>
 </table>
 == 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/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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 38: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Thioredoxin-disulfide reductase]]
+[[Category: Ko TP]]
-[[Category: Ko, T P]]
+[[Category: Lo YC]]
-[[Category: Lo, Y C]]
+[[Category: Wang AHJ]]
-[[Category: Wang, A H.J]]
-[[Category: Alternative splicing]]
-[[Category: Cytoplasm]]
-[[Category: Electron transport]]
-[[Category: Fad]]
-[[Category: Flavoprotein]]
-[[Category: Nadp]]
-[[Category: Nucleus]]
-[[Category: Oxidoreductase]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Redox-active center]]
-[[Category: Rossmann fold]]
-[[Category: Selenium]]
-[[Category: Selenocysteine]]
-[[Category: Transport]]

2zzc: Difference between revisions

Revision as of 14:03, 1 November 2023

Crystal structure of NADP(H):human thioredoxin reductase I

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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