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== | ==Crystal structure of the human Liver X receptor beta ligand binding domain in complex with a synthetic agonist== | ||
LXRbeta belongs to the nuclear hormone receptor superfamily of | <StructureSection load='1upw' size='340' side='right'caption='[[1upw]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1upw]] 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=1UPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UPW 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]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=444:N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE'>444</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=1upw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1upw OCA], [https://pdbe.org/1upw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1upw RCSB], [https://www.ebi.ac.uk/pdbsum/1upw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1upw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). | |||
== 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/up/1upw_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=1upw ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
LXRbeta belongs to the nuclear hormone receptor superfamily of ligand-activated transcription factors. Its natural ligands are supposed to be oxidised derivatives of cholesterol. Stimulation of LXRbeta by agonists activates a number of genes that are involved in the regulation of lipid metabolism and cholesterol efflux from cells. Therefore, LXRbeta may represent a novel therapeutic target for the treatment of dyslipidemia and atherosclerosis.Here, we report the X-ray crystal structure of the LXRbeta ligand-binding domain in complex with a synthetic agonist, T-0901317. This compound occupies the ligand-binding pocket of the receptor, forms numerous lipophilic contacts with the protein and one crucial hydrogen bond to His435 and stabilises the agonist conformation of the receptor ligand-binding domain. The recruitment of the AF2-region of the protein is not achieved via direct polar interactions of the ligand with protein side-chains of this helical segment, but rather via few hydrophobic contacts and probably more importantly via indirect effects involving the pre-orientation of side-chains that surround the ligand-binding pocket and form the interface to the AF2-helix.On the basis of these results we propose a binding mode and a mechanism of action for the putative natural ligands, oxidised derivatives of cholesterol. | |||
Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist.,Hoerer S, Schmid A, Heckel A, Budzinski RM, Nar H J Mol Biol. 2003 Dec 12;334(5):853-61. PMID:14643652<ref>PMID:14643652</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1upw" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Liver X receptor|Liver X receptor]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Budzinski | [[Category: Budzinski RM]] | ||
[[Category: Heckel | [[Category: Heckel A]] | ||
[[Category: Hoerer | [[Category: Hoerer S]] | ||
[[Category: Nar | [[Category: Nar H]] | ||
[[Category: Schmid | [[Category: Schmid A]] | ||