1uhl: Difference between revisions
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|PDB= 1uhl |SIZE=350|CAPTION= <scene name='initialview01'>1uhl</scene>, resolution 2.90Å | |PDB= 1uhl |SIZE=350|CAPTION= <scene name='initialview01'>1uhl</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
|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> | |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>, <scene name='pdbligand=MEI:(2E,4E)-11-METHOXY-3,7,11-TRIMETHYLDODECA-2,4-DIENOIC+ACID'>MEI</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uhl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uhl OCA], [http://www.ebi.ac.uk/pdbsum/1uhl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uhl RCSB]</span> | |||
}} | }} | ||
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[[Category: Svensson, S.]] | [[Category: Svensson, S.]] | ||
[[Category: Zachrisson, K.]] | [[Category: Zachrisson, K.]] | ||
[[Category: ligand-binding domain]] | [[Category: ligand-binding domain]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:10:25 2008'' | ||
Revision as of 21:10, 30 March 2008
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| 1uhl, resolution 2.90Å | |||||||||||||
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| Ligands: | 444, MEI | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| 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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