1p8d

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(New page: 200px<br /> <applet load="1p8d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p8d, resolution 2.8&Aring;" /> '''X-Ray Crystal Struct...)
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[[Image:1p8d.gif|left|200px]]<br />
 
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<applet load="1p8d" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1p8d, resolution 2.8&Aring;" />
 
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'''X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol'''<br />
 
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==Overview==
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==X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol==
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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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<StructureSection load='1p8d' size='340' side='right'caption='[[1p8d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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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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</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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<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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<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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==About this Structure==
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==See Also==
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1P8D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CO1 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1P8D OCA].
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*[[Liver X receptor|Liver X receptor]]
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__TOC__
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==Reference==
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</StructureSection>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=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://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:40:55 2007''
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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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