View source for 4ll1


==The structure of the TRX and TXNIP complex==
<StructureSection load='4ll1' size='340' side='right'caption='[[4ll1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ll1]] 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=4LL1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LL1 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]] 2&#8491;</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=4ll1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ll1 OCA], [https://pdbe.org/4ll1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ll1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ll1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ll1 ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== 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>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hwang J]]
[[Category: Kim MH]]