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- | [[Image:3r8d.jpg|left|200px]] | |
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- | <!--
| + | ==Activation of the Human Nuclear Xenobiotic Receptor PXR by the Reverse Transcriptase-Targeted Anti-HIV Drug PNU-142721== |
- | The line below this paragraph, containing "STRUCTURE_3r8d", creates the "Structure Box" on the page.
| + | <StructureSection load='3r8d' size='340' side='right'caption='[[3r8d]], [[Resolution|resolution]] 2.80Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3r8d]] 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=3R8D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R8D FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
- | -->
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PNU:6-CHLORO-2-(1-FURO[2,3-C]PYRIDIN-5-YL-ETHYLSULFANYL)-PYRIMIDIN-4-YLAMINE'>PNU</scene></td></tr> |
- | {{STRUCTURE_3r8d| PDB=3r8d | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8d OCA], [https://pdbe.org/3r8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r8d RCSB], [https://www.ebi.ac.uk/pdbsum/3r8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8d ProSAT]</span></td></tr> |
| + | </table> |
| + | == 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> |
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- | ===Activation of the Human Nuclear Xenobiotic Receptor PXR by the Reverse Transcriptase-Targeted Anti-HIV Drug PNU-142721=== | + | ==See Also== |
- | | + | *[[Pregnane X receptor 3D structures|Pregnane X receptor 3D structures]] |
- | | + | == References == |
- | <!--
| + | <references/> |
- | The line below this paragraph, {{ABSTRACT_PUBMED_21805522}}, adds the Publication Abstract to the page
| + | __TOC__ |
- | (as it appears on PubMed at http://www.pubmed.gov), where 21805522 is the PubMed ID number.
| + | </StructureSection> |
- | -->
| + | |
- | {{ABSTRACT_PUBMED_21805522}}
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- | | + | |
- | ==About this Structure==
| + | |
- | [[3r8d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R8D OCA]. | + | |
- | | + | |
- | ==Reference== | + | |
- | <ref group="xtra">PMID:021805522</ref><references group="xtra"/> | + | |
- | [[Category: Histone acetyltransferase]]
| + | |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Cheng, Y.]] | + | [[Category: Large Structures]] |
- | [[Category: Redinbo, M R.]] | + | [[Category: Cheng Y]] |
- | [[Category: Endobiotic]] | + | [[Category: Redinbo MR]] |
- | [[Category: Ligand binding domain]]
| + | |
- | [[Category: Nuclear receptor]]
| + | |
- | [[Category: Pxr]]
| + | |
- | [[Category: Transcription]]
| + | |
- | [[Category: Transcription regulation]]
| + | |
- | [[Category: Xenobiotic]]
| + | |
- | [[Category: Xenobiotic]]
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| Structural highlights
Function
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.[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998 Sep 1;102(5):1016-23. PMID:9727070 doi:10.1172/JCI3703
- ↑ Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson JR Jr, Schuetz EG, Boguski MS. The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics. 2001 Oct;11(7):555-72. PMID:11668216
- ↑ Geick A, Eichelbaum M, Burk O. Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. PMID:11297522 doi:10.1074/jbc.M010173200
- ↑ Li Y, Ross-Viola JS, Shay NF, Moore DD, Ricketts ML. Human CYP3A4 and murine Cyp3A11 are regulated by equol and genistein via the pregnane X receptor in a species-specific manner. J Nutr. 2009 May;139(5):898-904. doi: 10.3945/jn.108.103572. Epub 2009 Mar 18. PMID:19297428 doi:10.3945/jn.108.103572
- ↑ Watkins RE, Maglich JM, Moore LB, Wisely GB, Noble SM, Davis-Searles PR, Lambert MH, Kliewer SA, Redinbo MR. 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry. 2003 Feb 18;42(6):1430-8. PMID:12578355 doi:10.1021/bi0268753
- ↑ Teotico DG, Bischof JJ, Peng L, Kliewer SA, Redinbo MR. Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Mol Pharmacol. 2008 Dec;74(6):1512-20. doi: 10.1124/mol.108.050732. Epub 2008 Sep, 2. PMID:18768384 doi:10.1124/mol.108.050732
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