2p1v
From Proteopedia
(New page: 200px<br /> <applet load="2p1v" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p1v, resolution 2.200Å" /> '''Crystal structure ...) |
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| - | [[Image:2p1v. | + | [[Image:2p1v.jpg|left|200px]]<br /><applet load="2p1v" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2p1v, resolution 2.200Å" /> | caption="2p1v, resolution 2.200Å" /> | ||
'''Crystal structure of the ligand binding domain of the retinoid X receptor alpha in complex with 3-(2'-propoxy)-tetrahydronaphtyl cinnamic acid and a fragment of the coactivator TIF-2'''<br /> | '''Crystal structure of the ligand binding domain of the retinoid X receptor alpha in complex with 3-(2'-propoxy)-tetrahydronaphtyl cinnamic acid and a fragment of the coactivator TIF-2'''<br /> | ||
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| + | ==Overview== | ||
| + | Retinoid X receptors (RXRalpha, -beta, and -gamma) occupy a central, position in the nuclear receptor superfamily, because they form, heterodimers with many other family members and hence are involved in the, control of a variety of (patho)physiologic processes. Selective RXR, ligands, referred to as rexinoids, are already used or are being developed, for cancer therapy and have promise for the treatment of metabolic, diseases. However, important side effects remain associated with existing, rexinoids. Here we describe the rational design and functional, characterization of a spectrum of RXR modulators ranging from partial to, pure antagonists and demonstrate their utility as tools to probe the, implication of RXRs in cell biological phenomena. One of these ligands, renders RXR activity particularly sensitive to coactivator levels and has, the potential to act as a cell-specific RXR modulator. A combination of, crystallographic and fluorescence anisotropy studies reveals the molecular, details accounting for the agonist-to-antagonist transition and provides, direct experimental evidence for a correlation between the pharmacological, activity of a ligand and its impact on the structural dynamics of the, activation helix H12. Using RXR and its cognate ligands as a model system, our correlative analysis of 3D structures and dynamic data provides an, original view on ligand actions and enables the establishment of, mechanistic concepts, which will aid in the development of selective, nuclear receptor modulators. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2P1V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 5TN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2P1V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=5TN:'>5TN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P1V OCA]. |
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| + | ==Reference== | ||
| + | Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function., Nahoum V, Perez E, Germain P, Rodriguez-Barrios F, Manzo F, Kammerer S, Lemaire G, Hirsch O, Royer CA, Gronemeyer H, de Lera AR, Bourguet W, Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17323-8. Epub 2007 Oct 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17947383 17947383] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:04:22 2008'' |
Revision as of 10:04, 23 January 2008
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Crystal structure of the ligand binding domain of the retinoid X receptor alpha in complex with 3-(2'-propoxy)-tetrahydronaphtyl cinnamic acid and a fragment of the coactivator TIF-2
Overview
Retinoid X receptors (RXRalpha, -beta, and -gamma) occupy a central, position in the nuclear receptor superfamily, because they form, heterodimers with many other family members and hence are involved in the, control of a variety of (patho)physiologic processes. Selective RXR, ligands, referred to as rexinoids, are already used or are being developed, for cancer therapy and have promise for the treatment of metabolic, diseases. However, important side effects remain associated with existing, rexinoids. Here we describe the rational design and functional, characterization of a spectrum of RXR modulators ranging from partial to, pure antagonists and demonstrate their utility as tools to probe the, implication of RXRs in cell biological phenomena. One of these ligands, renders RXR activity particularly sensitive to coactivator levels and has, the potential to act as a cell-specific RXR modulator. A combination of, crystallographic and fluorescence anisotropy studies reveals the molecular, details accounting for the agonist-to-antagonist transition and provides, direct experimental evidence for a correlation between the pharmacological, activity of a ligand and its impact on the structural dynamics of the, activation helix H12. Using RXR and its cognate ligands as a model system, our correlative analysis of 3D structures and dynamic data provides an, original view on ligand actions and enables the establishment of, mechanistic concepts, which will aid in the development of selective, nuclear receptor modulators.
About this Structure
2P1V is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function., Nahoum V, Perez E, Germain P, Rodriguez-Barrios F, Manzo F, Kammerer S, Lemaire G, Hirsch O, Royer CA, Gronemeyer H, de Lera AR, Bourguet W, Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17323-8. Epub 2007 Oct 18. PMID:17947383
Page seeded by OCA on Wed Jan 23 12:04:22 2008
