1ot7
From Proteopedia
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|PDB= 1ot7 |SIZE=350|CAPTION= <scene name='initialview01'>1ot7</scene>, resolution 2.90Å | |PDB= 1ot7 |SIZE=350|CAPTION= <scene name='initialview01'>1ot7</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CHC:6-ETHYL-CHENODEOXYCHOLIC+ACID'>CHC</scene>, <scene name='pdbligand=IU5:ISO-URSODEOXYCHOLIC+ACID'>IU5</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |GENE= NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1osv|1OSV]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ot7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ot7 OCA], [http://www.ebi.ac.uk/pdbsum/1ot7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ot7 RCSB]</span> | ||
}} | }} | ||
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[[Category: Rastinejad, F.]] | [[Category: Rastinejad, F.]] | ||
[[Category: Willson, T M.]] | [[Category: Willson, T M.]] | ||
| - | [[Category: CHC]] | ||
| - | [[Category: IU5]] | ||
[[Category: bile acid]] | [[Category: bile acid]] | ||
[[Category: coactivator]] | [[Category: coactivator]] | ||
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[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:50:01 2008'' |
Revision as of 19:50, 30 March 2008
| |||||||
| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | NR1H4 (Rattus norvegicus) | ||||||
| Related: | 1OSV
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR
Overview
The nuclear receptor FXR is the sensor of physiological levels of enterohepatic bile acids, the end products of cholesterol catabolism. Here we report crystal structures of the FXR ligand binding domain in complex with coactivator peptide and two different bile acids. An unusual A/B ring juncture, a feature associated with bile acids and no other steroids, provides ligand discrimination and triggers a pi-cation switch that activates FXR. Helix 12, the activation function 2 of the receptor, adopts the agonist conformation and stabilizes coactivator peptide binding. FXR is able to interact simultaneously with two coactivator motifs, providing a mechanism for enhanced binding of coactivators through intermolecular contacts between their LXXLL sequences. These FXR complexes provide direct insights into the design of therapeutic bile acids for treatment of hyperlipidemia and cholestasis.
About this Structure
1OT7 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for bile acid binding and activation of the nuclear receptor FXR., Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, Rastinejad F, Mol Cell. 2003 Apr;11(4):1093-100. PMID:12718893
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