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1p8d

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[[Image:1p8d.gif|left|200px]]
[[Image:1p8d.gif|left|200px]]
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{{Structure
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|PDB= 1p8d |SIZE=350|CAPTION= <scene name='initialview01'>1p8d</scene>, resolution 2.8&Aring;
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The line below this paragraph, containing "STRUCTURE_1p8d", creates the "Structure Box" on the page.
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|SITE=
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|LIGAND= <scene name='pdbligand=CO1:17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-3-OL'>CO1</scene>
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|GENE= NR1H2 OR LXRB OR UNR OR NER ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_1p8d| PDB=1p8d | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8d OCA], [http://www.ebi.ac.uk/pdbsum/1p8d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1p8d RCSB]</span>
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'''X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol'''
'''X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol'''
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[[Category: Willson, T M.]]
[[Category: Willson, T M.]]
[[Category: Wisely, B.]]
[[Category: Wisely, B.]]
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[[Category: epoxycholesterol]]
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[[Category: Epoxycholesterol]]
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[[Category: liver x receptor]]
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[[Category: Liver x receptor]]
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[[Category: lxr]]
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[[Category: Lxr]]
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[[Category: nuclear receptor]]
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[[Category: Nuclear receptor]]
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[[Category: steroid receptor]]
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[[Category: Steroid receptor]]
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[[Category: transcription]]
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[[Category: Transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:48:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:56:21 2008''
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Revision as of 01:48, 3 May 2008

Image:1p8d.gif

Template:STRUCTURE 1p8d

X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol


Overview

The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidinetryptophan switch that holds the receptor in its active conformation. Hydrogen bonding interactions with the ligand act to position the His-435 imidazole ring against the Trp-457 indole ring, allowing an electrostatic interaction that holds the AF2 helix in the active position. The neutral oxysterol 24(S),25-epoxycholesterol accepts a hydrogen bond from His-435 that positions the imidazole ring of the histidine above the pyrrole ring of the tryptophan. In contrast, the acidic T0901317 hydroxyl group makes a shorter hydrogen bond with His-435 that pulls the imidazole over the electron-rich benzene ring of the tryptophan, possibly strengthening the electrostatic interaction. Point mutagenesis of Trp-457 supports the observation that the ligand-histidine-tryptophan coupling is different between the two ligands. The lipophilic liver X receptor ligand-binding pocket is larger than the corresponding steroid hormone receptors, which allows T0901317 to adopt two distinct conformations. These results provide a molecular basis for liver X receptor activation by a wide range of endogenous neutral and acidic ligands.

About this Structure

1P8D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch., Williams S, Bledsoe RK, Collins JL, Boggs S, Lambert MH, Miller AB, Moore J, McKee DD, Moore L, Nichols J, Parks D, Watson M, Wisely B, Willson TM, J Biol Chem. 2003 Jul 18;278(29):27138-43. Epub 2003 May 7. PMID:12736258 Page seeded by OCA on Sat May 3 04:48:45 2008

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