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[[Image: | ==WILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL== | ||
<StructureSection load='1qku' size='340' side='right' caption='[[1qku]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1qku]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The September 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Estrogen Receptor'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_9 10.2210/rcsb_pdb/mom_2003_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QKU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QKU FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EST:ESTRADIOL'>EST</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hcp|1hcp]], [[1hcq|1hcq]], [[1akf|1akf]], [[1a52|1a52]], [[1ere|1ere]], [[1err|1err]], [[3erd|3erd]], [[3ert|3ert]], [[1qkm|1qkm]], [[1qkn|1qkn]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qku OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qku RCSB], [http://www.ebi.ac.uk/pdbsum/1qku PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qk/1qku_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The crystal structure of a triple cysteine to serine mutant ERalpha ligand-binding domain (LBD), complexed with estradiol, shows that despite the presence of a tightly bound agonist ligand, the protein exhibits an antagonist-like conformation, similar to that observed in raloxifen and 4-hydroxytamoxifen-bound structures. This mutated receptor binds estradiol with wild type affinity and displays transcriptional activity upon estradiol stimulation, but with limited potency (about 50%). This partial activity is efficiently repressed in antagonist competition assays. The comparison with available LBD structures reveals key features governing the positioning of helix H12 and highlights the importance of cysteine residues in promoting an active conformation. Furthermore the present study reveals a hydrogen bond network connecting ligand binding to protein trans conformation. These observations support a dynamic view of H12 positioning, where the control of the equilibrium between two stable locations determines the partial agonist character of a given ligand. | |||
Crystal structure of a mutant hERalpha ligand-binding domain reveals key structural features for the mechanism of partial agonism.,Gangloff M, Ruff M, Eiler S, Duclaud S, Wurtz JM, Moras D J Biol Chem. 2001 May 4;276(18):15059-65. Epub 2001 Feb 6. PMID:11278577<ref>PMID:11278577</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Estrogen receptor|Estrogen receptor]] | *[[Estrogen receptor|Estrogen receptor]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Estrogen Receptor]] | [[Category: Estrogen Receptor]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
Revision as of 03:15, 29 September 2014
WILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOLWILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe crystal structure of a triple cysteine to serine mutant ERalpha ligand-binding domain (LBD), complexed with estradiol, shows that despite the presence of a tightly bound agonist ligand, the protein exhibits an antagonist-like conformation, similar to that observed in raloxifen and 4-hydroxytamoxifen-bound structures. This mutated receptor binds estradiol with wild type affinity and displays transcriptional activity upon estradiol stimulation, but with limited potency (about 50%). This partial activity is efficiently repressed in antagonist competition assays. The comparison with available LBD structures reveals key features governing the positioning of helix H12 and highlights the importance of cysteine residues in promoting an active conformation. Furthermore the present study reveals a hydrogen bond network connecting ligand binding to protein trans conformation. These observations support a dynamic view of H12 positioning, where the control of the equilibrium between two stable locations determines the partial agonist character of a given ligand. Crystal structure of a mutant hERalpha ligand-binding domain reveals key structural features for the mechanism of partial agonism.,Gangloff M, Ruff M, Eiler S, Duclaud S, Wurtz JM, Moras D J Biol Chem. 2001 May 4;276(18):15059-65. Epub 2001 Feb 6. PMID:11278577[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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