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==Crystal structure of human Retinoid X receptor alpha ligand binding domain complex with UAB113 and coactivator peptide GRIP-1==
<StructureSection load='7uw4' size='340' side='right'caption='[[7uw4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7uw4]] is a 2 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=7UW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UW4 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OI5:(2E,4E,6Z,8E)-3,7-dimethyl-8-[2-(3-methylbutyl)-3-propylcyclohex-2-en-1-ylidene]octa-2,4,6-trienoic+acid'>OI5</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=7uw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uw4 OCA], [https://pdbe.org/7uw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uw4 RCSB], [https://www.ebi.ac.uk/pdbsum/7uw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uw4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RXRA_HUMAN RXRA_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.<ref>PMID:10195690</ref> <ref>PMID:11162439</ref> <ref>PMID:11915042</ref> <ref>PMID:20215566</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Compound 1 is a potent rexinoid that is highly effective in cancer chemoprevention but elevates serum triglycerides. In an effort to separate the lipid toxicity from the anticancer activity of 1, we synthesized four new analogs of rexinoid 1, of which three rexinoids did not elevate serum triglycerides. Rexinoids 3 and 4 are twice as potent as rexinoid 1 in binding to Retinoid X receptor (RXR). All-trans retinoic acid (ATRA) plays a key role in maintaining skin homeostasis, and rexinoids 3-6 are highly effective in upregulating the genes responsible for the biosynthesis of ATRA. Inflammation plays a key role in skin cancer, and rexinoids 3 and 4 are highly effective in diminishing LPS-induced inflammation. Rexinoids 3 and 4 are highly effective in preventing UVB-induced nonmelanoma skin cancer (NMSC) without displaying any overt toxicities. Biophysical studies of rexinoids 3 and 5 bound to hRXRalpha-ligand binding domain (LBD) reveal important conformational and dynamical differences in the ligand binding domain.

Conformationally Defined Rexinoids for the Prevention of Inflammation and Nonmelanoma Skin Cancers.,Atigadda VR, Kashyap MP, Yang Z, Chattopadhyay D, Melo N, Sinha R, Belyaeva OV, Chou CF, Chang PL, Kedishvili NY, Grubbs CJ, Renfrow MB, Muccio DD, Elmets CA, Athar M J Med Chem. 2022 Nov 10;65(21):14409-14423. doi: 10.1021/acs.jmedchem.2c00735. , Epub 2022 Nov 1. PMID:36318154<ref>PMID:36318154</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7uw4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Atigadda V]]
[[Category: Chattopadhyay D]]
[[Category: Yang Z]]