3fal: Difference between revisions

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-[[Image:3fal.png|left|200px]]
-{{STRUCTURE_3fal|  PDB=3fal  |  SCENE=  }}
+==humanRXR alpha & mouse LXR alpha complexed with Retenoic acid and GSK2186==
+<StructureSection load='3fal' size='340' side='right'caption='[[3fal]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3fal]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FAL 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]] 2.36&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LO2:2-{4-[BUTYL(3-CHLORO-4,5-DIMETHOXYBENZYL)AMINO]PHENYL}-1,1,1,3,3,3-HEXAFLUOROPROPAN-2-OL'>LO2</scene>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</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=3fal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fal OCA], [https://pdbe.org/3fal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fal RCSB], [https://www.ebi.ac.uk/pdbsum/3fal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fal 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fa/3fal_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fal ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A cocrystal structure of T1317 (3) bound to hLXRbeta was utilized in the design of a series of substituted N-phenyl tertiary amines. Profiling in binding and functional assays led to the identification of LXR modulator GSK9772 ( 20) as a high-affinity LXRbeta ligand (IC 50 = 30 nM) that shows separation of anti-inflammatory and lipogenic activities in human macrophage and liver cell lines, respectively. A cocrystal structure of the structurally related analog 19 bound to LXRbeta reveals regions within the receptor that can affect receptor modulation through ligand modification. Mechanistic studies demonstrate that 20 is greater than 10-fold selective for LXR-mediated transrepression of proinflammatory gene expression versus transactivation of lipogenic signaling pathways, thus providing an opportunity for the identification of LXR modulators with improved therapeutic indexes.
-===humanRXR alpha & mouse LXR alpha complexed with Retenoic acid and GSK2186===
+Structure-guided design of N-phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity.,Chao EY, Caravella JA, Watson MA, Campobasso N, Ghisletti S, Billin AN, Galardi C, Wang P, Laffitte BA, Iannone MA, Goodwin BJ, Nichols JA, Parks DJ, Stewart E, Wiethe RW, Williams SP, Smallwood A, Pearce KH, Glass CK, Willson TM, Zuercher WJ, Collins JL J Med Chem. 2008 Sep 25;51(18):5758-65. PMID:18800767<ref>PMID:18800767</ref>
-{{ABSTRACT_PUBMED_18800767}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3fal" style="background-color:#fffaf0;"></div>
-[[3fal]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FAL OCA].
 ==See Also==
-*[[Retinoid X receptor|Retinoid X receptor]]
+*[[Liver X receptor|Liver X receptor]]
+*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:018800767</ref><references group="xtra"/>
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Billin, A N.]]
+[[Category: Billin AN]]
-[[Category: Campobasso, N.]]
+[[Category: Campobasso N]]
-[[Category: Caravella, J A.]]
+[[Category: Caravella JA]]
-[[Category: Chao, E Y.]]
+[[Category: Chao EY]]
-[[Category: Collins, J L.]]
+[[Category: Collins JL]]
-[[Category: Galardi, C.]]
+[[Category: Galardi C]]
-[[Category: Ghisletti, S.]]
+[[Category: Ghisletti S]]
-[[Category: Watson, M A.]]
+[[Category: Watson MA]]
-[[Category: Willson, T M.]]
+[[Category: Willson TM]]
-[[Category: Zuercher, W J.]]
+[[Category: Zuercher WJ]]
-[[Category: Dna-binding]]
-[[Category: Host-virus interaction]]
-[[Category: Metal-binding]]
-[[Category: Nuclear hormone receptor nonsteroidal lxr agonist choloestorol metabolism]]
-[[Category: Nucleus]]
-[[Category: Receptor]]
-[[Category: Signaling protein]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Zinc-finger]]