2p15: Difference between revisions

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==Overview==

The steroid hormone receptors are characterized by binding to relatively, rigid, inflexible endogenous steroid ligands. Other members of the nuclear, receptor superfamily bind to conformationally flexible lipids and show a, corresponding degree of elasticity in the ligand-binding pocket. Here, we, report the X-ray crystal structure of the oestrogen receptor alpha, (ERalpha) bound to an oestradiol derivative with a prosthetic group, ortho- trifluoromethlyphenylvinyl, which binds in a novel extended pocket, in the ligand-binding domain. Unlike ER antagonists with bulky side, groups, this derivative is enclosed in the ligand-binding pocket, and acts, as a potent agonist. This work shows that steroid hormone receptors can, interact with a wider array of pharmacophores than previously thought, through structural plasticity in the ligand-binding pocket.

The steroid hormone receptors are characterized by binding to relatively rigid, inflexible endogenous steroid ligands. Other members of the nuclear receptor superfamily bind to conformationally flexible lipids and show a corresponding degree of elasticity in the ligand-binding pocket. Here, we report the X-ray crystal structure of the oestrogen receptor alpha (ERalpha) bound to an oestradiol derivative with a prosthetic group, ortho- trifluoromethlyphenylvinyl, which binds in a novel extended pocket in the ligand-binding domain. Unlike ER antagonists with bulky side groups, this derivative is enclosed in the ligand-binding pocket, and acts as a potent agonist. This work shows that steroid hormone receptors can interact with a wider array of pharmacophores than previously thought through structural plasticity in the ligand-binding pocket.

==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==

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[[Category: Homo sapiens]]

[[Category: Protein complex]]

[[Category: Bruning, J.B.]]

[[Category: Bruning, J B.]]

[[Category: Greene, G.L.]]

[[Category: Greene, G L.]]

[[Category: Kim, Y.]]

[[Category: Nettles, K.W.]]

[[Category: Nettles, K W.]]

[[Category: EZT]]

[[Category: helix 12]]

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[[Category: nulear receptor]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-The steroid hormone receptors are characterized by binding to relatively, rigid, inflexible endogenous steroid ligands. Other members of the nuclear, receptor superfamily bind to conformationally flexible lipids and show a, corresponding degree of elasticity in the ligand-binding pocket. Here, we, report the X-ray crystal structure of the oestrogen receptor alpha, (ERalpha) bound to an oestradiol derivative with a prosthetic group, ortho- trifluoromethlyphenylvinyl, which binds in a novel extended pocket, in the ligand-binding domain. Unlike ER antagonists with bulky side, groups, this derivative is enclosed in the ligand-binding pocket, and acts, as a potent agonist. This work shows that steroid hormone receptors can, interact with a wider array of pharmacophores than previously thought, through structural plasticity in the ligand-binding pocket.
+The steroid hormone receptors are characterized by binding to relatively rigid, inflexible endogenous steroid ligands. Other members of the nuclear receptor superfamily bind to conformationally flexible lipids and show a corresponding degree of elasticity in the ligand-binding pocket. Here, we report the X-ray crystal structure of the oestrogen receptor alpha (ERalpha) bound to an oestradiol derivative with a prosthetic group, ortho- trifluoromethlyphenylvinyl, which binds in a novel extended pocket in the ligand-binding domain. Unlike ER antagonists with bulky side groups, this derivative is enclosed in the ligand-binding pocket, and acts as a potent agonist. This work shows that steroid hormone receptors can interact with a wider array of pharmacophores than previously thought through structural plasticity in the ligand-binding pocket.
+==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==
@@ Line 13: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Bruning, J.B.]]
+[[Category: Bruning, J B.]]
-[[Category: Greene, G.L.]]
+[[Category: Greene, G L.]]
 [[Category: Kim, Y.]]
-[[Category: Nettles, K.W.]]
+[[Category: Nettles, K W.]]
 [[Category: EZT]]
 [[Category: helix 12]]
@@ Line 22: / Line 25: @@
 [[Category: nulear receptor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:28:54 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:43 2008''