1qkt
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystal structure of a triple cysteine to serine mutant ERalpha | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
[[Category: Ruff, M.]] | [[Category: Ruff, M.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
| - | [[Category: Wurtz, J | + | [[Category: Wurtz, J M.]] |
[[Category: EST]] | [[Category: EST]] | ||
[[Category: agonism]] | [[Category: agonism]] | ||
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[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:40:43 2008'' |
Revision as of 12:40, 21 February 2008
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MUTANT ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this Structure
1QKT is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 14:40:43 2008
Categories: Homo sapiens | Single protein | Duclaud, S. | Eiler, S. | Gangloff, M. | Moras, D. | Ruff, M. | SPINE, Structural Proteomics in Europe. | Wurtz, J M. | EST | Agonism | Antagonism | Crystal structure | Estradiol receptor | Spine | Steroid | Structural genomics | Structural proteomics in europe
