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[[Image:2acl.gif|left|200px]]


{{Structure
==Liver X-Receptor alpha Ligand Binding Domain with SB313987==
|PDB= 2acl |SIZE=350|CAPTION= <scene name='initialview01'>2acl</scene>, resolution 2.8&Aring;
<StructureSection load='2acl' size='340' side='right'caption='[[2acl]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=L05:1-BENZYL-3-(4-METHOXYPHENYLAMINO)-4-PHENYLPYRROLE-2,5-DIONE'>L05</scene>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</scene>
<table><tr><td colspan='2'>[[2acl]] is a 8 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=2ACL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ACL FirstGlance]. <br>
|ACTIVITY=
</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>
|GENE= RXRA, NR2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), Nr1h3, Lxra ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L05:1-BENZYL-3-(4-METHOXYPHENYLAMINO)-4-PHENYLPYRROLE-2,5-DIONE'>L05</scene>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2acl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2acl OCA], [https://pdbe.org/2acl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2acl RCSB], [https://www.ebi.ac.uk/pdbsum/2acl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2acl ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2acl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2acl OCA], [http://www.ebi.ac.uk/pdbsum/2acl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2acl RCSB]</span>
== 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/ac/2acl_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=2acl ConSurf].
<div style="clear:both"></div>


'''Liver X-Receptor alpha Ligand Binding Domain with SB313987'''
==See Also==
 
*[[Liver X receptor|Liver X receptor]]
 
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
==Overview==
== References ==
Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 as an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.
<references/>
 
__TOC__
==About this Structure==
</StructureSection>
2ACL is a [[Protein complex]] structure of sequences 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=2ACL OCA].
 
==Reference==
Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure., Jaye MC, Krawiec JA, Campobasso N, Smallwood A, Qiu C, Lu Q, Kerrigan JJ, De Los Frailes Alvaro M, Laffitte B, Liu WS, Marino JP Jr, Meyer CR, Nichols JA, Parks DJ, Perez P, Sarov-Blat L, Seepersaud SD, Steplewski KM, Thompson SK, Wang P, Watson MA, Webb CL, Haigh D, Caravella JA, Macphee CH, Willson TM, Collins JL, J Med Chem. 2005 Aug 25;48(17):5419-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16107141 16107141]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Campobasso N]]
[[Category: Campobasso, N.]]
[[Category: Jaye MC]]
[[Category: Jaye, M C.]]
[[Category: Kerrigan JJ]]
[[Category: Kerrigan, J J.]]
[[Category: Krawiec JA]]
[[Category: Krawiec, J A.]]
[[Category: Lu Q]]
[[Category: Lu, Q.]]
[[Category: Qiu C]]
[[Category: Qiu, C.]]
[[Category: Smallwood A]]
[[Category: Smallwood, A.]]
[[Category: nuclear hormone receptor ligand binding domain transcription factor three layered a-helix fold]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:50:50 2008''

Latest revision as of 12:12, 14 February 2024

Liver X-Receptor alpha Ligand Binding Domain with SB313987Liver X-Receptor alpha Ligand Binding Domain with SB313987

Structural highlights

2acl is a 8 chain structure with sequence from Homo sapiens and Mus musculus. 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

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.[1] [2] [3] [4]

Evolutionary Conservation

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

See Also

References

  1. ↑ Gorla-Bajszczak A, Juge-Aubry C, Pernin A, Burger AG, Meier CA. Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):37-47. PMID:10195690
  2. ↑ Harish S, Ashok MS, Khanam T, Rangarajan PN. Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function. Biochem Biophys Res Commun. 2000 Dec 29;279(3):853-7. PMID:11162439 doi:10.1006/bbrc.2000.4043
  3. ↑ Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002 Apr;35(4):937-46. PMID:11915042 doi:10.1053/jhep.2002.32470
  4. ↑ Santos NC, Kim KH. Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar , 9. PMID:20215566 doi:10.1210/en.2009-1338

2acl, resolution 2.80Å

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