1xv9: Difference between revisions
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|PDB= 1xv9 |SIZE=350|CAPTION= <scene name='initialview01'>1xv9</scene>, resolution 2.7Å | |PDB= 1xv9 |SIZE=350|CAPTION= <scene name='initialview01'>1xv9</scene>, resolution 2.7Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CI2:(5BETA)-PREGNANE-3,20-DIONE'>CI2</scene> | |LIGAND= <scene name='pdbligand=CI2:(5BETA)-PREGNANE-3,20-DIONE'>CI2</scene>, <scene name='pdbligand=F15:PENTADECANOIC+ACID'>F15</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= RXRA, NR2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= RXRA, NR2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xv9 OCA], [http://www.ebi.ac.uk/pdbsum/1xv9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xv9 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wisely, B B.]] | [[Category: Wisely, B B.]] | ||
[[Category: Xu, R X.]] | [[Category: Xu, R X.]] | ||
[[Category: car]] | [[Category: car]] | ||
[[Category: pregnanedione]] | [[Category: pregnanedione]] | ||
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[[Category: src1]] | [[Category: src1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:55:10 2008'' | ||
Revision as of 00:55, 31 March 2008
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| , resolution 2.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | RXRA, NR2B1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid, and 5b-pregnane-3,20-dione.
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.
About this StructureAbout this Structure
1XV9 is a Protein complex structure of sequences from Homo sapiens. 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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