1ot7
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1ot7.gif|left|200px]] | + | [[Image:1ot7.gif|left|200px]] |
| - | + | ||
| - | '''Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR''' | + | {{Structure |
| + | |PDB= 1ot7 |SIZE=350|CAPTION= <scene name='initialview01'>1ot7</scene>, resolution 2.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=IU5:ISO-URSODEOXYCHOLIC+ACID'>IU5</scene> and <scene name='pdbligand=CHC:6-ETHYL-CHENODEOXYCHOLIC ACID'>CHC</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | }} | ||
| + | |||
| + | '''Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1OT7 is a [ | + | 1OT7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OT7 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12718893 12718893] |
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 29: | Line 38: | ||
[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:15:16 2008'' |
Revision as of 11:15, 20 March 2008
| |||||||
| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | NR1H4 (Rattus norvegicus) | ||||||
| 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
Page seeded by OCA on Thu Mar 20 13:15:16 2008
