1m13
From Proteopedia
(Difference between revisions)
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<StructureSection load='1m13' size='340' side='right'caption='[[1m13]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='1m13' size='340' side='right'caption='[[1m13]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1m13]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1m13]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M13 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYF:4-HYDROXY-5-ISOBUTYRYL-6-METHYL-1,3,7-TRIS-(3-METHYL-BUT-2-ENYL)-6-(4-METHYL-PENT-3-ENYL)-BICYCLO[3.3.1]NON-3-ENE-2,9-DIONE'>HYF</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYF:4-HYDROXY-5-ISOBUTYRYL-6-METHYL-1,3,7-TRIS-(3-METHYL-BUT-2-ENYL)-6-(4-METHYL-PENT-3-ENYL)-BICYCLO[3.3.1]NON-3-ENE-2,9-DIONE'>HYF</scene></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=1m13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m13 OCA], [https://pdbe.org/1m13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m13 RCSB], [https://www.ebi.ac.uk/pdbsum/1m13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m13 ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [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=1m13 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=1m13 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 activated by a wide variety of clinically used drugs and serves as a master regulator of drug metabolism and excretion gene expression in mammals. St. John's wort is used widely in Europe and the United States to treat depression. This unregulated herbal remedy leads to dangerous drug-drug interactions, however, in patients taking oral contraceptives, antivirals, or immunosuppressants. Such interactions are caused by the activation of the human PXR by hyperforin, the psychoactive agent in St. John's wort. In this study, we show that hyperforin induces the expression of numerous drug metabolism and excretion genes in primary human hepatocytes. We present the 2.1 A crystal structure of hyperforin in complex with the ligand binding domain of human PXR. Hyperforin induces conformational changes in PXR's ligand binding pocket relative to structures of human PXR elucidated previously and increases the size of the pocket by 250 A(3). We find that the mutation of individual aromatic residues within the ligand binding cavity changes PXR's response to particular ligands. Taken together, these results demonstrate that PXR employs structural flexibility to expand the chemical space it samples and that the mutation of specific residues within the ligand binding pocket of PXR tunes the receptor's response to ligands. | ||
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| - | 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin.,Watkins RE, Maglich JM, Moore LB, Wisely GB, Noble SM, Davis-Searles PR, Lambert MH, Kliewer SA, Redinbo MR Biochemistry. 2003 Feb 18;42(6):1430-8. PMID:12578355<ref>PMID:12578355</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1m13" 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]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Davis-Searles | + | [[Category: Davis-Searles PR]] |
| - | [[Category: Kliewer | + | [[Category: Kliewer SA]] |
| - | [[Category: Lambert | + | [[Category: Lambert MH]] |
| - | [[Category: Maglich | + | [[Category: Maglich JM]] |
| - | [[Category: Moore | + | [[Category: Moore LB]] |
| - | [[Category: Noble | + | [[Category: Noble SM]] |
| - | [[Category: Redinbo | + | [[Category: Redinbo MR]] |
| - | [[Category: Watkins | + | [[Category: Watkins RE]] |
| - | [[Category: Wisely | + | [[Category: Wisely GB]] |
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Current revision
Crystal Structure of the Human Pregane X Receptor Ligand Binding Domain in Complex with Hyperforin, a Constituent of St. John's Wort
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