View source for 1upw

[[Image:1upw.jpg|left|200px]]

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{{STRUCTURE_1upw|  PDB=1upw  |  SCENE=  }} 

'''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 [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==
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: Single protein]]
[[Category: Budzinski, R M.]]
[[Category: Heckel, A.]]
[[Category: Hoerer, S.]]
[[Category: Nar, H.]]
[[Category: Schmid, A.]]
[[Category: Crystal structure]]
[[Category: Ligand binding domain]]
[[Category: Liver x receptor]]
[[Category: Nuclear hormone receptor]]
[[Category: Transcription factor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 11:33:05 2008''