View source for 4gfx


==Crystal structure of the N-terminal domain of TXNIP==
<StructureSection load='4gfx' size='340' side='right'caption='[[4gfx]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gfx]] is a 1 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=4GFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GFX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4gfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gfx OCA], [https://pdbe.org/4gfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gfx RCSB], [https://www.ebi.ac.uk/pdbsum/4gfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gfx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TXNIP_HUMAN TXNIP_HUMAN] May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).<ref>PMID:17603038</ref> <ref>PMID:12821938</ref> <ref>PMID:18541147</ref> <ref>PMID:21460850</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The redox-dependent inhibition of thioredoxin (TRX) by thioredoxin-interacting protein (TXNIP) plays a pivotal role in various cancers and metabolic syndromes. However, the molecular mechanism of this regulation is largely unknown. Here, we present the crystal structure of the TRX-TXNIP complex and demonstrate that the inhibition of TRX by TXNIP is mediated by an intermolecular disulphide interaction resulting from a novel disulphide bond-switching mechanism. Upon binding to TRX, TXNIP undergoes a structural rearrangement that involves switching of a head-to-tail interprotomer Cys63-Cys247 disulphide between TXNIP molecules to an interdomain Cys63-Cys190 disulphide, and the formation of a de novo intermolecular TXNIP Cys247-TRX Cys32 disulphide. This disulphide-switching event unexpectedly results in a domain arrangement of TXNIP that is entirely different from those of other arrestin family proteins. We further show that the intermolecular disulphide bond between TRX and TXNIP dissociates in the presence of high concentrations of reactive oxygen species. This study provides insight into TRX and TXNIP-dependent cellular regulation.

The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein.,Hwang J, Suh HW, Jeon YH, Hwang E, Nguyen LT, Yeom J, Lee SG, Lee C, Kim KJ, Kang BS, Jeong JO, Oh TK, Choi I, Lee JO, Kim MH Nat Commun. 2014 Jan 6;5:2958. doi: 10.1038/ncomms3958. PMID:24389582<ref>PMID:24389582</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gfx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hwang J]]
[[Category: Kim MH]]