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| {{STRUCTURE_1upw| PDB=1upw | SCENE= }} | | {{STRUCTURE_1upw| PDB=1upw | SCENE= }} |
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| '''CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST'''
| | ===CRYSTAL STRUCTURE OF THE HUMAN LIVER X RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH A SYNTHETIC AGONIST=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14643652}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14643652 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14643652}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Nuclear hormone receptor]] | | [[Category: Nuclear hormone receptor]] |
| [[Category: Transcription factor]] | | [[Category: Transcription factor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:33:05 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:27:42 2008'' |
