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1uhl

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[[Image:1uhl.gif|left|200px]]<br /><applet load="1uhl" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1uhl.gif|left|200px]]
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caption="1uhl, resolution 2.90&Aring;" />
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'''Crystal structure of the LXRalfa-RXRbeta LBD heterodimer'''<br />
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{{Structure
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|PDB= 1uhl |SIZE=350|CAPTION= <scene name='initialview01'>1uhl</scene>, resolution 2.90&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=444:N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE'>444</scene> and <scene name='pdbligand=MEI:(2E,4E)-11-METHOXY-3,7,11-TRIMETHYLDODECA-2,4-DIENOIC ACID'>MEI</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''Crystal structure of the LXRalfa-RXRbeta LBD heterodimer'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1UHL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=444:'>444</scene> and <scene name='pdbligand=MEI:'>MEI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UHL OCA].
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1UHL is a [[Protein complex]] structure of sequences 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=1UHL OCA].
==Reference==
==Reference==
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Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation., Svensson S, Ostberg T, Jacobsson M, Norstrom C, Stefansson K, Hallen D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L, EMBO J. 2003 Sep 15;22(18):4625-33. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12970175 12970175]
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Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation., Svensson S, Ostberg T, Jacobsson M, Norstrom C, Stefansson K, Hallen D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L, EMBO J. 2003 Sep 15;22(18):4625-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12970175 12970175]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: ligand-binding domain]]
[[Category: ligand-binding domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:24:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:32:06 2008''

Revision as of 12:32, 20 March 2008


PDB ID 1uhl

Drag the structure with the mouse to rotate
, resolution 2.90Å
Ligands: and
Coordinates: save as pdb, mmCIF, xml



Crystal structure of the LXRalfa-RXRbeta LBD heterodimer


Overview

The nuclear receptor heterodimers of liver X receptor (LXR) and retinoid X receptor (RXR) are key transcriptional regulators of genes involved in lipid homeostasis and inflammation. We report the crystal structure of the ligand-binding domains (LBDs) of LXRalpha and RXRbeta complexed to the synthetic LXR agonist T-0901317 and the RXR agonist methoprene acid (Protein Data Base entry 1UHL). Both LBDs are in agonist conformation with GRIP-1 peptides bound at the coactivator binding sites. T-0901317 occupies the center of the LXR ligand-binding pocket and its hydroxyl head group interacts with H421 and W443, residues identified by mutational analysis as critical for ligand-induced transcriptional activation by T-0901317 and various endogenous oxysterols. The topography of the pocket suggests a common anchoring of these oxysterols via their 22-, 24- or 27-hydroxyl group to H421 and W443. Polyunsaturated fatty acids act as LXR antagonists and an E267A mutation was found to enhance their transcriptional inhibition. The present structure provides a powerful tool for the design of novel modulators that can be used to characterize further the physiological functions of the LXR-RXR heterodimer.

About this Structure

1UHL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation., Svensson S, Ostberg T, Jacobsson M, Norstrom C, Stefansson K, Hallen D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L, EMBO J. 2003 Sep 15;22(18):4625-33. PMID:12970175

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