1mvc: Difference between revisions
New page: left|200px<br /> <applet load="1mvc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mvc, resolution 1.9Å" /> '''Crystal structure of... |
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[[Image:1mvc.gif|left|200px]]<br /> | [[Image:1mvc.gif|left|200px]]<br /><applet load="1mvc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1mvc, resolution 1.9Å" /> | caption="1mvc, resolution 1.9Å" /> | ||
'''Crystal structure of the human RXR alpha ligand binding domain bound to the synthetic agonist compound BMS 649 and a coactivator peptide'''<br /> | '''Crystal structure of the human RXR alpha ligand binding domain bound to the synthetic agonist compound BMS 649 and a coactivator peptide'''<br /> | ||
==Overview== | ==Overview== | ||
The nuclear receptor RXR is an obligate partner in many signal | The nuclear receptor RXR is an obligate partner in many signal transduction pathways. We report the high-resolution structures of two complexes of the human RXRalpha ligand-binding domain specifically bound to two different and chemically unrelated agonist compounds: docosa hexaenoic acid, a natural derivative of eicosanoic acid, present in mammalian cells and recently identified as a potential endogenous RXR ligand in the mouse brain, and the synthetic ligand BMS 649. In both structures the RXR-ligand-binding domain forms homodimers and exhibits the active conformation previously observed with 9-cis-RA. Analysis of the differences in ligand-protein contacts (predominantly van der Waals forces) and binding cavity geometries and volumes for the several agonist-bound RXR structures clarifies the structural features important for ligand recognition. The L-shaped ligand-binding pocket adapts to the diverse ligands, especially at the level of residue N306, which might thus constitute a new target for drug-design. Despite its highest affinity 9-cis-RA displays the lowest number of ligand-protein contacts. These structural results support the idea that docosa hexaenoic acid and related fatty acids could be natural agonists of RXRs and question the real nature of the endogenous ligand(s) in mammalian cells. | ||
==About this Structure== | ==About this Structure== | ||
1MVC 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 BM6 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1MVC 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=BM6:'>BM6</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MVC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Egea, P | [[Category: Egea, P F.]] | ||
[[Category: Mitschler, A.]] | [[Category: Mitschler, A.]] | ||
[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:24 2008'' | ||
Revision as of 14:59, 21 February 2008
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Crystal structure of the human RXR alpha ligand binding domain bound to the synthetic agonist compound BMS 649 and a coactivator peptide
OverviewOverview
The nuclear receptor RXR is an obligate partner in many signal transduction pathways. We report the high-resolution structures of two complexes of the human RXRalpha ligand-binding domain specifically bound to two different and chemically unrelated agonist compounds: docosa hexaenoic acid, a natural derivative of eicosanoic acid, present in mammalian cells and recently identified as a potential endogenous RXR ligand in the mouse brain, and the synthetic ligand BMS 649. In both structures the RXR-ligand-binding domain forms homodimers and exhibits the active conformation previously observed with 9-cis-RA. Analysis of the differences in ligand-protein contacts (predominantly van der Waals forces) and binding cavity geometries and volumes for the several agonist-bound RXR structures clarifies the structural features important for ligand recognition. The L-shaped ligand-binding pocket adapts to the diverse ligands, especially at the level of residue N306, which might thus constitute a new target for drug-design. Despite its highest affinity 9-cis-RA displays the lowest number of ligand-protein contacts. These structural results support the idea that docosa hexaenoic acid and related fatty acids could be natural agonists of RXRs and question the real nature of the endogenous ligand(s) in mammalian cells.
About this StructureAbout this Structure
1MVC is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Molecular recognition of agonist ligands by RXRs., Egea PF, Mitschler A, Moras D, Mol Endocrinol. 2002 May;16(5):987-97. PMID:11981034
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