1xnx: Difference between revisions
New page: left|200px<br /><applet load="1xnx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xnx, resolution 2.90Å" /> '''Crystal structure of... |
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[[Image:1xnx.gif|left|200px]]<br /><applet load="1xnx" size=" | [[Image:1xnx.gif|left|200px]]<br /><applet load="1xnx" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1xnx, resolution 2.90Å" /> | caption="1xnx, resolution 2.90Å" /> | ||
'''Crystal structure of constitutive androstane receptor'''<br /> | '''Crystal structure of constitutive androstane receptor'''<br /> | ||
==Overview== | ==Overview== | ||
The nuclear receptor CAR is a xenobiotic responsive transcription factor | 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. | ||
==About this Structure== | ==About this Structure== | ||
1XNX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ATE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1XNX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ATE:'>ATE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XNX OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: nuclear receptor; crystal structure]] | [[Category: nuclear receptor; crystal structure]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:56:48 2008'' | ||
Revision as of 16:56, 21 February 2008
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Crystal structure of constitutive androstane receptor
OverviewOverview
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.
About this StructureAbout this Structure
1XNX is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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
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