1osh

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[[Image:1osh.jpg|left|200px]]<br /><applet load="1osh" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1osh.jpg|left|200px]]
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caption="1osh, resolution 1.80&Aring;" />
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'''A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR'''<br />
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{{Structure
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|PDB= 1osh |SIZE=350|CAPTION= <scene name='initialview01'>1osh</scene>, resolution 1.80&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=FEX:METHYL 3-{3-[(CYCLOHEXYLCARBONYL){[4'-(DIMETHYLAMINO)BIPHENYL-4-YL]METHYL}AMINO]PHENYL}ACRYLATE'>FEX</scene>
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|ACTIVITY=
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|GENE= NR1H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1OSH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FEX:'>FEX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].
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1OSH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSH OCA].
==Reference==
==Reference==
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A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR., Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM, Mol Cell. 2003 Apr;11(4):1079-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12718892 12718892]
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A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR., Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM, Mol Cell. 2003 Apr;11(4):1079-92. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12718892 12718892]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: nuclear receptor]]
[[Category: nuclear receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:21:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:15:02 2008''

Revision as of 11:15, 20 March 2008

Image:1osh.jpg


PDB ID 1osh

Drag the structure with the mouse to rotate
, resolution 1.80Å
Ligands:
Gene: NR1H4 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR


Contents

Overview

The farnesoid X receptor (FXR) functions as a bile acid (BA) sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. However, BAs are poor reagents for characterizing FXR functions due to multiple receptor independent properties. Accordingly, using combinatorial chemistry we evolved a small molecule agonist termed fexaramine with 100-fold increased affinity relative to natural compounds. Gene-profiling experiments conducted in hepatocytes with FXR-specific fexaramine versus the primary BA chenodeoxycholic acid (CDCA) produced remarkably distinct genomic targets. Highly diffracting cocrystals (1.78 A) of fexaramine bound to the ligand binding domain of FXR revealed the agonist sequestered in a 726 A(3) hydrophobic cavity and suggest a mechanistic basis for the initial step in the BA signaling pathway. The discovery of fexaramine will allow us to unravel the FXR genetic network from the BA network and selectively manipulate components of the cholesterol pathway that may be useful in treating cholesterol-related human diseases.

Disease

Known disease associated with this structure: Breast cancer, susceptibility to OMIM:[601593]

About this Structure

1OSH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR., Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM, Mol Cell. 2003 Apr;11(4):1079-92. PMID:12718892

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