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{{STRUCTURE_3ipq|  PDB=3ipq  |  SCENE=  }}
===X-ray structure of GW3965 synthetic agonist bound to the LXR-alpha===
{{ABSTRACT_PUBMED_20382159}}


==Disease==
==X-ray structure of GW3965 synthetic agonist bound to the LXR-alpha==
[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.  
<StructureSection load='3ipq' size='340' side='right'caption='[[3ipq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ipq]] 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=3IPQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IPQ 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=965:[3-(3-{[2-CHLORO-3-(TRIFLUOROMETHYL)BENZYL](2,2-DIPHENYLETHYL)AMINO}PROPOXY)PHENYL]ACETIC+ACID'>965</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3ipq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ipq OCA], [https://pdbe.org/3ipq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ipq RCSB], [https://www.ebi.ac.uk/pdbsum/3ipq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ipq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NR1H3_HUMAN NR1H3_HUMAN] Orphan receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating 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/ip/3ipq_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=3ipq ConSurf].
<div style="clear:both"></div>


==Function==
==See Also==
[[http://www.uniprot.org/uniprot/NR1H3_HUMAN NR1H3_HUMAN]] Orphan receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref><ref>PMID:7481822</ref><ref>PMID:9223431</ref><ref>PMID:9296499</ref><ref>PMID:9223281</ref><ref>PMID:10449719</ref><ref>PMID:12954634</ref>
*[[Liver X receptor|Liver X receptor]]
 
__TOC__
==About this Structure==
</StructureSection>
[[3ipq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IPQ OCA].
 
==Reference==
<ref group="xtra">PMID:020382159</ref><references group="xtra"/><references/>
[[Category: Histone acetyltransferase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bennet, D J.]]
[[Category: Large Structures]]
[[Category: Cooke, A J.]]
[[Category: Bennet DJ]]
[[Category: Fradera, X.]]
[[Category: Cooke AJ]]
[[Category: Haunso, A.]]
[[Category: Fradera X]]
[[Category: Hosfield, D.]]
[[Category: Haunso A]]
[[Category: King, A.]]
[[Category: Hosfield D]]
[[Category: McGuire, R.]]
[[Category: King A]]
[[Category: Nimz, O.]]
[[Category: McGuire R]]
[[Category: Skene, R.]]
[[Category: Nimz O]]
[[Category: Uitdehaag, J C.M.]]
[[Category: Skene R]]
[[Category: Vu, D.]]
[[Category: Uitdehaag JCM]]
[[Category: Wijnands, R.]]
[[Category: Vu D]]
[[Category: Activator]]
[[Category: Wijnands R]]
[[Category: Acyltransferase]]
[[Category: Dna-binding]]
[[Category: Isopeptide bond]]
[[Category: Lxr homodimer]]
[[Category: Lxr signaling]]
[[Category: Metal-binding]]
[[Category: Nuclear receptor]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Proto-oncogene]]
[[Category: Receptor]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Transferase]]
[[Category: Zinc-finger]]

Latest revision as of 13:06, 21 February 2024

X-ray structure of GW3965 synthetic agonist bound to the LXR-alphaX-ray structure of GW3965 synthetic agonist bound to the LXR-alpha

Structural highlights

3ipq is a 2 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 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NR1H3_HUMAN Orphan receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating 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

3ipq, resolution 2.00Å

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