1qkt: Difference between revisions
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:54:13 2007'' | ||
