1p8d

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[[Image:1p8d.gif|left|200px]]
 
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{{Structure
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==X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol==
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|PDB= 1p8d |SIZE=350|CAPTION= <scene name='initialview01'>1p8d</scene>, resolution 2.8&Aring;
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<StructureSection load='1p8d' size='340' side='right'caption='[[1p8d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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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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<table><tr><td colspan='2'>[[1p8d]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P8D FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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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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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8d OCA], [https://pdbe.org/1p8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p8d RCSB], [https://www.ebi.ac.uk/pdbsum/1p8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8d ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p8/1p8d_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1p8d ConSurf].
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<div style="clear:both"></div>
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'''X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol'''
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==See Also==
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*[[Liver X receptor|Liver X receptor]]
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__TOC__
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==Overview==
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</StructureSection>
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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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==About this Structure==
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1P8D is a [[Protein complex]] structure of sequences 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=1P8D OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12736258 12736258]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bledsoe, R K.]]
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[[Category: Bledsoe RK]]
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[[Category: Boggs, S.]]
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[[Category: Boggs S]]
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[[Category: Collins, J L.]]
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[[Category: Collins JL]]
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[[Category: Lambert, M H.]]
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[[Category: Lambert MH]]
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[[Category: McKee, D D.]]
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[[Category: McKee DD]]
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[[Category: Miller, A B.]]
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[[Category: Miller AB]]
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[[Category: Moore, J.]]
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[[Category: Moore J]]
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[[Category: Moore, L.]]
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[[Category: Moore L]]
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[[Category: Nichols, J.]]
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[[Category: Nichols J]]
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[[Category: Parks, D.]]
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[[Category: Parks D]]
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[[Category: Watson, M.]]
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[[Category: Watson M]]
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[[Category: Williams, S.]]
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[[Category: Williams S]]
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[[Category: Willson, T M.]]
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[[Category: Willson TM]]
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[[Category: Wisely, B.]]
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[[Category: Wisely B]]
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[[Category: CO1]]
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[[Category: epoxycholesterol]]
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[[Category: liver x receptor]]
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[[Category: lxr]]
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[[Category: nuclear receptor]]
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[[Category: steroid receptor]]
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[[Category: transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:21:12 2008''
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Current revision

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

PDB ID 1p8d

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