1ot7

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[[Image:1ot7.gif|left|200px]]
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{{STRUCTURE_1ot7| PDB=1ot7 | SCENE= }}
{{STRUCTURE_1ot7| PDB=1ot7 | SCENE= }}
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'''Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR'''
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===Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12718893 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12718893}}
==About this Structure==
==About this Structure==
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[[Category: Ligand binding domain]]
[[Category: Ligand binding domain]]
[[Category: Nuclear receptor]]
[[Category: Nuclear receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:15:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:45:43 2008''

Revision as of 13:45, 27 July 2008

Image:1ot7.png

Template:STRUCTURE 1ot7

Structural Basis for 3-deoxy-CDCA Binding and Activation of FXR

Template:ABSTRACT PUBMED 12718893

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 Sun Jul 27 16:45:43 2008

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