1upw: Difference between revisions
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[[Image:1upw.jpg|left|200px]] | [[Image:1upw.jpg|left|200px]] | ||
'''CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST''' | {{Structure | ||
|PDB= 1upw |SIZE=350|CAPTION= <scene name='initialview01'>1upw</scene>, resolution 2.40Å | |||
|SITE= <scene name='pdbsite=AC1:444+Binding+Site+For+Chain+A'>AC1</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> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1UPW is a [ | 1UPW is a [[Single protein]] structure of 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=1UPW OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist., Hoerer S, Schmid A, Heckel A, Budzinski RM, Nar H, J Mol Biol. 2003 Dec 12;334(5):853-61. PMID:[http:// | Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist., Hoerer S, Schmid A, Heckel A, Budzinski RM, Nar H, J Mol Biol. 2003 Dec 12;334(5):853-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14643652 14643652] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:35:18 2008'' | ||
Revision as of 12:35, 20 March 2008
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| 1upw, resolution 2.40Å | |||||||||||||
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| Sites: | AC1 | ||||||||||||
| Ligands: | 444 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST
Overview
LXRbeta belongs to the nuclear hormone receptor superfamily of ligand-activated transcription factors. Its natural ligands are supposed to be oxidised derivatives of cholesterol. Stimulation of LXRbeta by agonists activates a number of genes that are involved in the regulation of lipid metabolism and cholesterol efflux from cells. Therefore, LXRbeta may represent a novel therapeutic target for the treatment of dyslipidemia and atherosclerosis.Here, we report the X-ray crystal structure of the LXRbeta ligand-binding domain in complex with a synthetic agonist, T-0901317. This compound occupies the ligand-binding pocket of the receptor, forms numerous lipophilic contacts with the protein and one crucial hydrogen bond to His435 and stabilises the agonist conformation of the receptor ligand-binding domain. The recruitment of the AF2-region of the protein is not achieved via direct polar interactions of the ligand with protein side-chains of this helical segment, but rather via few hydrophobic contacts and probably more importantly via indirect effects involving the pre-orientation of side-chains that surround the ligand-binding pocket and form the interface to the AF2-helix.On the basis of these results we propose a binding mode and a mechanism of action for the putative natural ligands, oxidised derivatives of cholesterol.
About this Structure
1UPW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist., Hoerer S, Schmid A, Heckel A, Budzinski RM, Nar H, J Mol Biol. 2003 Dec 12;334(5):853-61. PMID:14643652
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