1p8d

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{{STRUCTURE_1p8d| PDB=1p8d | SCENE= }}
{{STRUCTURE_1p8d| PDB=1p8d | SCENE= }}
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'''X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol'''
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===X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_12736258}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12736258 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12736258}}
==About this Structure==
==About this Structure==
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[[Category: Steroid receptor]]
[[Category: Steroid receptor]]
[[Category: Transcription]]
[[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 Mon Jul 28 18:52:34 2008''

Revision as of 15:52, 28 July 2008

Image:1p8d.png

Template:STRUCTURE 1p8d

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

Template:ABSTRACT PUBMED 12736258

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

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