3r8d: Difference between revisions

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<StructureSection load='3r8d' size='340' side='right'caption='[[3r8d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='3r8d' size='340' side='right'caption='[[3r8d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3r8d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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>
<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>
</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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1I2, PXR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=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>
<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>
</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> 
[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human pregnane X receptor (PXR) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. PXR responds to a structurally diverse variety of endogenous and xenobiotic compounds, and coordinates the expression of genes central to the metabolism and excretion of potentially harmful chemicals, including human therapeutics. The reverse transcriptase inhibitor PNU-142721 has been designed to treat human immunodeficiency virus (HIV) infection. Although this compound has anti-HIV activity, it was established using cell-based assays that PNU-142721 is an efficacious PXR agonist. We present here the 2.8 A resolution crystal structure of the human PXR ligand-binding domain in complex with PNU-142721. PXR employs one hydrogen bond and fourteen van der Waals contacts to interact with the ligand, but allows two loops adjacent to the ligand-binding pocket to remain disordered in the structure. These observations highlight the role structural flexibility plays in PXR's promiscuous responses to xenobiotics. The crystal structure also explains why PNU-173575, a thiomethyl metabolite of PNU-142721, exhibits enhanced PXR activation relative to the unmodified compound and why PNU-142721 can also activate rat PXR. Taken together, the results presented here elucidate the structural basis for PXR activation by PNU-142721 and related chemicals.
 
Activation of the human nuclear xenobiotic receptor PXR by the reverse transcriptase-targeted anti-HIV drug PNU-142721.,Cheng Y, Redinbo MR Protein Sci. 2011 Jul 29. doi: 10.1002/pro.706. PMID:21805522<ref>PMID:21805522</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3r8d" 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: Histone acetyltransferase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Cheng, Y]]
[[Category: Cheng Y]]
[[Category: Redinbo, M R]]
[[Category: Redinbo MR]]
[[Category: Endobiotic]]
[[Category: Ligand binding domain]]
[[Category: Nuclear receptor]]
[[Category: Pxr]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Xenobiotic]]

Latest revision as of 10:52, 21 February 2024

Activation of the Human Nuclear Xenobiotic Receptor PXR by the Reverse Transcriptase-Targeted Anti-HIV Drug PNU-142721

3r8d, resolution 2.80Å

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