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[[Image:1pqc.gif|left|200px]]<br /><applet load="1pqc" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1pqc, resolution 2.80&Aring;" />
'''HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317'''<br />


==Overview==
==HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317==
The structures of the liver X receptor LXRbeta (NR1H2) have been determined in complexes with two synthetic ligands, T0901317 and GW3965, to 2.1 and 2.4 A, respectively. Together with its isoform LXRalpha (NR1H3) it regulates target genes involved in metabolism and transport of cholesterol and fatty acids. The two LXRbeta structures reveal a flexible ligand-binding pocket that can adjust to accommodate fundamentally different ligands. The ligand-binding pocket is hydrophobic but with polar or charged residues at the two ends of the cavity. T0901317 takes advantage of this by binding to His-435 close to H12 while GW3965 orients itself with its charged group in the opposite direction. Both ligands induce a fixed "agonist conformation" of helix H12 (also called the AF-2 domain), resulting in a transcriptionally active receptor.
<StructureSection load='1pqc' size='340' side='right'caption='[[1pqc]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pqc]] 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=1PQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PQC 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]] 2.8&#8491;</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=1pqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pqc OCA], [https://pdbe.org/1pqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pqc RCSB], [https://www.ebi.ac.uk/pdbsum/1pqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pqc 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/pq/1pqc_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=1pqc ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1PQC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=444:'>444</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PQC OCA].
*[[Liver X receptor|Liver X receptor]]
 
__TOC__
==Reference==
</StructureSection>
The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands., Farnegardh M, Bonn T, Sun S, Ljunggren J, Ahola H, Wilhelmsson A, Gustafsson JA, Carlquist M, J Biol Chem. 2003 Oct 3;278(40):38821-8. Epub 2003 Jun 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12819202 12819202]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Ahola, H.]]
[[Category: Ahola H]]
[[Category: Bonn, T.]]
[[Category: Bonn T]]
[[Category: Carlquist, M.]]
[[Category: Carlquist M]]
[[Category: Farnegardh, M.]]
[[Category: Farnegardh M]]
[[Category: Gustafsson, J A.]]
[[Category: Gustafsson J-A]]
[[Category: Ljunggren, J.]]
[[Category: Ljunggren J]]
[[Category: Sun, S.]]
[[Category: Sun S]]
[[Category: Wilhelmsson, A.]]
[[Category: Wilhelmsson A]]
[[Category: 444]]
[[Category: lxrb+t0901317]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:31:28 2008''

Latest revision as of 11:10, 14 February 2024

HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317

Structural highlights

1pqc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1pqc, resolution 2.80Å

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