3hvl
From Proteopedia
(Difference between revisions)
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<StructureSection load='3hvl' size='340' side='right'caption='[[3hvl]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='3hvl' size='340' side='right'caption='[[3hvl]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3hvl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3hvl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3ctc 3ctc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HVL FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SRL:[2-(3,5-DI-TERT-BUTYL-4-HYDROXY-PHENYL)-1-(DIETHOXY-PHOSPHORYL)-VINYL]-PHOSPHONIC+ACID+DIETHLYL+ESTER'>SRL</scene></td></tr> | |
| - | <tr id=' | + | |
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hvl OCA], [https://pdbe.org/3hvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hvl RCSB], [https://www.ebi.ac.uk/pdbsum/3hvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hvl ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hvl OCA], [https://pdbe.org/3hvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hvl RCSB], [https://www.ebi.ac.uk/pdbsum/3hvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hvl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children. | ||
== Function == | == Function == | ||
| - | [[https://www.uniprot.org/uniprot/NR1I2_HUMAN NR1I2_HUMAN | + | [https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref> [https://www.uniprot.org/uniprot/NR1I2_HUMAN NR1I2_HUMAN] Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.<ref>PMID:9727070</ref> <ref>PMID:11668216</ref> <ref>PMID:11297522</ref> <ref>PMID:19297428</ref> <ref>PMID:12578355</ref> <ref>PMID:18768384</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hvl ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hvl ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The nuclear xenobiotic receptor PXR is a ligand-inducible transcription factor regulating drug-metabolizing enzymes and transporters and a master switch mediating potentially adverse drug-drug interactions. In addition to binding a coactivator protein such as SRC-1, the C-terminal ligand-binding domain (LBD) is solely responsible for ligand recognition and thus the ligand-dependent downstream effects. In an effort to facilitate structural studies of PXR to understand and abolish the interactions between PXR and its ligands, several recombinant PXR/SRC-1 constructs were designed and evaluated for expression, stability and activity. Expression strategies employing either dual expression or translationally coupled bicistronic expression were found to be unsuitable for producing stable PXR in a stochiometric complex with a peptide derived from SRC-1 (SRC-1p). A single polypeptide chain encompassing PXR and SRC-1p tethered with a peptidyl linker was designed to promote intramolecular complex formation. This tethered protein was overexpressed as a soluble protein and required no additional SRC-1p for further stabilization. X-ray crystal structures in the presence and absence of the known PXR agonist SR-12813 were determined to high resolution. In addition, a circular dichroism-based binding assay was developed to allow rapid evaluation of PXR ligand affinity, making this tethered protein a convenient and effective reagent for the rational attenuation of drug-induced PXR-mediated metabolism. | ||
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| - | Construction and characterization of a fully active PXR/SRC-1 tethered protein with increased stability.,Wang W, Prosise WW, Chen J, Taremi SS, Le HV, Madison V, Cui X, Thomas A, Cheng KC, Lesburg CA Protein Eng Des Sel. 2008 Jul;21(7):425-33. Epub 2008 May 2. PMID:18456871<ref>PMID:18456871</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3hvl" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Pregnane X receptor|Pregnane X receptor]] | + | *[[Pregnane X receptor 3D structures|Pregnane X receptor 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
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[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Chen | + | [[Category: Chen J]] |
| - | [[Category: Cheng | + | [[Category: Cheng KC]] |
| - | [[Category: Cui | + | [[Category: Cui X]] |
| - | [[Category: Le | + | [[Category: Le HV]] |
| - | [[Category: Lesburg | + | [[Category: Lesburg CA]] |
| - | [[Category: Madison | + | [[Category: Madison V]] |
| - | [[Category: Prosise | + | [[Category: Prosise WW]] |
| - | [[Category: Taremi | + | [[Category: Taremi SS]] |
| - | [[Category: Thomas | + | [[Category: Thomas A]] |
| - | [[Category: Wang | + | [[Category: Wang W]] |
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Current revision
Tethered PXR-LBD/SRC-1p complexed with SR-12813
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Categories: Homo sapiens | Large Structures | Chen J | Cheng KC | Cui X | Le HV | Lesburg CA | Madison V | Prosise WW | Taremi SS | Thomas A | Wang W
