1xnx

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[[Image:1xnx.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_1xnx| PDB=1xnx | SCENE= }}
{{STRUCTURE_1xnx| PDB=1xnx | SCENE= }}
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'''Crystal structure of constitutive androstane receptor'''
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===Crystal structure of constitutive androstane receptor===
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==Overview==
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The nuclear receptor CAR is a xenobiotic responsive transcription factor that plays a central role in the clearance of drugs and bilirubin while promoting cocaine and acetaminophen toxicity. In addition, CAR has established a "reverse" paradigm of nuclear receptor action where the receptor is active in the absence of ligand and inactive when bound to inverse agonists. We now report the crystal structure of murine CAR bound to the inverse agonist androstenol. Androstenol binds within the ligand binding pocket, but unlike many nuclear receptor ligands, it makes no contacts with helix H12/AF2. The transition from constitutive to basal activity (androstenol bound) appears to be associated with a ligand-induced kink between helices H10 and H11. This disrupts the previously predicted salt bridge that locks H12 in the transcriptionally active conformation. This mechanism of inverse agonism is distinct from traditional nuclear receptor antagonists thereby offering a new approach to receptor modulation.
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The line below this paragraph, {{ABSTRACT_PUBMED_15610734}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15610734 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15610734}}
==About this Structure==
==About this Structure==
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[[Category: Crystal structure]]
[[Category: Crystal structure]]
[[Category: Nuclear receptor]]
[[Category: Nuclear receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:16:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 09:09:53 2008''

Revision as of 06:09, 28 July 2008

Image:1xnx.png

Template:STRUCTURE 1xnx

Crystal structure of constitutive androstane receptor

Template:ABSTRACT PUBMED 15610734

About this Structure

1XNX is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Structure of the murine constitutive androstane receptor complexed to androstenol: a molecular basis for inverse agonism., Shan L, Vincent J, Brunzelle JS, Dussault I, Lin M, Ianculescu I, Sherman MA, Forman BM, Fernandez EJ, Mol Cell. 2004 Dec 22;16(6):907-17. PMID:15610734

Page seeded by OCA on Mon Jul 28 09:09:53 2008

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