1xvp: Difference between revisions
New page: left|200px<br /> <applet load="1xvp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xvp, resolution 2.6Å" /> '''crystal structure of... |
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[[Image:1xvp.gif|left|200px]]<br /> | [[Image:1xvp.gif|left|200px]]<br /><applet load="1xvp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1xvp, resolution 2.6Å" /> | caption="1xvp, resolution 2.6Å" /> | ||
'''crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCO'''<br /> | '''crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCO'''<br /> | ||
==Overview== | ==Overview== | ||
The X-ray crystal structure of the human constitutive androstane receptor | The X-ray crystal structure of the human constitutive androstane receptor (CAR, NR1I3)/retinoid X receptor alpha (RXRalpha, NR2B1) heterodimer sheds light on the mechanism of ligand-independent activation of transcription by nuclear receptors. CAR contains a single-turn Helix X that restricts the conformational freedom of the C-terminal AF2 helix, favoring the active state of the receptor. Helix X and AF2 sit atop four amino acids that shield the CAR ligand binding pocket. A fatty acid ligand was identified in the RXRalpha binding pocket. The endogenous RXRalpha ligand, combined with stabilizing interactions from the heterodimer interface, served to hold RXRalpha in an active conformation. The structure suggests that upon translocation, CAR/RXRalpha heterodimers are preorganized in an active conformation in cells such that they can regulate transcription of target genes. Insights into the molecular basis of CAR constitutive activity can be exploited in the design of inverse agonists as drugs for treatment of obesity. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1XVP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with F15 and CID as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1XVP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=F15:'>F15</scene> and <scene name='pdbligand=CID:'>CID</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XVP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Lambert, M | [[Category: Lambert, M H.]] | ||
[[Category: Moore, J | [[Category: Moore, J T.]] | ||
[[Category: Moore, L | [[Category: Moore, L B.]] | ||
[[Category: Waitt, G | [[Category: Waitt, G M.]] | ||
[[Category: Warren, E | [[Category: Warren, E N.]] | ||
[[Category: Weinert, E | [[Category: Weinert, E E.]] | ||
[[Category: Williams, J | [[Category: Williams, J D.]] | ||
[[Category: Willson, T | [[Category: Willson, T M.]] | ||
[[Category: Wisely, B | [[Category: Wisely, B B.]] | ||
[[Category: Xu, R | [[Category: Xu, R X.]] | ||
[[Category: CID]] | [[Category: CID]] | ||
[[Category: F15]] | [[Category: F15]] | ||
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[[Category: src1]] | [[Category: src1]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:59:08 2008'' | ||
Revision as of 16:59, 21 February 2008
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crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCO
OverviewOverview
The X-ray crystal structure of the human constitutive androstane receptor (CAR, NR1I3)/retinoid X receptor alpha (RXRalpha, NR2B1) heterodimer sheds light on the mechanism of ligand-independent activation of transcription by nuclear receptors. CAR contains a single-turn Helix X that restricts the conformational freedom of the C-terminal AF2 helix, favoring the active state of the receptor. Helix X and AF2 sit atop four amino acids that shield the CAR ligand binding pocket. A fatty acid ligand was identified in the RXRalpha binding pocket. The endogenous RXRalpha ligand, combined with stabilizing interactions from the heterodimer interface, served to hold RXRalpha in an active conformation. The structure suggests that upon translocation, CAR/RXRalpha heterodimers are preorganized in an active conformation in cells such that they can regulate transcription of target genes. Insights into the molecular basis of CAR constitutive activity can be exploited in the design of inverse agonists as drugs for treatment of obesity.
DiseaseDisease
Known diseases associated with this structure: Adrenocortical tumor, somatic OMIM:[188830], Carney complex, type 1 OMIM:[188830], Myxoma, intracardiac OMIM:[188830], Pigmented adrenocortical disease, primary, 1 OMIM:[188830], Spastic paraplegia-7 OMIM:[602783], Thyroid carcinoma, papillary OMIM:[188830]
About this StructureAbout this Structure
1XVP is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer., Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, Williams JD, Collins JL, Moore LB, Willson TM, Moore JT, Mol Cell. 2004 Dec 22;16(6):919-28. PMID:15610735
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