1qku: Difference between revisions

Revision as of 08:10, 13 April 2008

WILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL

OverviewOverview

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.

About this StructureAbout this Structure

1QKU is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1QKU with [Estrogen Receptor]. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun Apr 13 08:10:11 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1qku.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1qku |SIZE=350|CAPTION= <scene name='initialview01'>1qku</scene>, resolution 3.20&Aring;
+The line below this paragraph, containing "STRUCTURE_1qku", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Est+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Est+Binding+Site+For+Chain+B'>AC2</scene> and <scene name='pdbsite=AC3:Est+Binding+Site+For+Chain+C'>AC3</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=EST:ESTRADIOL'>EST</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1qku|  PDB=1qku  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<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.ebi.ac.uk/pdbsum/1qku PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qku RCSB]</span>
-}}
 '''WILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL'''
@@ Line 33: / Line 30: @@
 [[Category: SPINE, Structural Proteomics in Europe.]]
 [[Category: Wurtz, J M.]]
-[[Category: agonism]]
+[[Category: Agonism]]
-[[Category: antagonism]]
+[[Category: Antagonism]]
-[[Category: crystal structure]]
+[[Category: Crystal structure]]
-[[Category: estradiol receptor]]
+[[Category: Estradiol receptor]]
-[[Category: spine]]
+[[Category: Spine]]
-[[Category: steroid]]
+[[Category: Steroid]]
-[[Category: structural genomic]]
+[[Category: Structural genomic]]
-[[Category: structural proteomics in europe]]
+[[Category: Structural proteomics in europe]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Apr 13 08:10:11 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:15:07 2008''