1mvc: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1mvc.gif|left|200px]] | [[Image:1mvc.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1mvc", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_1mvc| PDB=1mvc | SCENE= }} | |||
}} | |||
'''Crystal structure of the human RXR alpha ligand binding domain bound to the synthetic agonist compound BMS 649 and a coactivator peptide''' | '''Crystal structure of the human RXR alpha ligand binding domain bound to the synthetic agonist compound BMS 649 and a coactivator peptide''' | ||
| Line 28: | Line 25: | ||
[[Category: Mitschler, A.]] | [[Category: Mitschler, A.]] | ||
[[Category: Moras, D.]] | [[Category: Moras, D.]] | ||
[[Category: | [[Category: Agonist recognition]] | ||
[[Category: | [[Category: Nuclear receptor]] | ||
[[Category: | [[Category: Retinoic acid]] | ||
[[Category: | [[Category: Transcription factor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:45:54 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 01:45, 3 May 2008
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. 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 Page seeded by OCA on Sat May 3 01:45:54 2008