6dup: Difference between revisions

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 ==CRYSTAL STRUCTURE OF PXR IN COMPLEX WITH COMPOUND 7==
-<StructureSection load='6dup' size='340' side='right' caption='[[6dup]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='6dup' size='340' side='right'caption='[[6dup]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6dup]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DUP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DUP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6dup]] is a 2 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=6DUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DUP FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HCJ:(2S)-2-({[3-(trifluoromethyl)[1,1-biphenyl]-4-yl]oxy}methyl)-2,3-dihydro-7H-[1,3]oxazolo[3,2-a]pyrimidin-7-one'>HCJ</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]] 2.3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1I2, PXR ([http://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=HCJ:(2S)-2-({[3-(trifluoromethyl)[1,1-biphenyl]-4-yl]oxy}methyl)-2,3-dihydro-7H-[1,3]oxazolo[3,2-a]pyrimidin-7-one'>HCJ</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dup OCA], [http://pdbe.org/6dup PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dup RCSB], [http://www.ebi.ac.uk/pdbsum/6dup PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dup 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=6dup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dup OCA], [https://pdbe.org/6dup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dup RCSB], [https://www.ebi.ac.uk/pdbsum/6dup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dup ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 ==
-This work describes the rational amelioration of Cytochrome P450 4/5 (CYP3A4/5) induction through the Pregnane-X Receptor (PXR) pathway in a series of compounds that modulate the metabotropic glutamate Receptor 2 (mGluR2) via an allosteric mechanism. The compounds were initially shown to induce CYP3A4/5 via the gold-standard induction assay measured in primary human hepatocytes. This was followed up by testing the compounds in a PXR assay which correlated well with the assay in primary cells. Further, one of the compounds was crystallized with PXR (pdb code 6DUP). Analysis of this co-crystal structure, together with previously published PXR co-crystal structures, lead to modification ideas. The compounds synthesized based on these ideas were shown not to be CYP3A4/5 inducers. The mGluR2 activity of the resulting compounds was maintained.
-Amelioration of PXR-mediated CYP3A4 induction by mGluR2 modulators.,Vaz RJ, Li Y, Chellaraj V, Reiling S, Kuntzweiler T, Yang D, Shen H, Batchelor JD, Zhang Y, Chen X, McLean LR, Kosley R Jr Bioorg Med Chem Lett. 2018 Aug 20. pii: S0960-894X(18)30696-6. doi:, 10.1016/j.bmcl.2018.08.022. PMID:30146095<ref>PMID:30146095</ref>
+==See Also==
+*[[Pregnane X receptor 3D structures|Pregnane X receptor 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6dup" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Chen, X]]
+[[Category: Large Structures]]
-[[Category: Mclean, L R]]
+[[Category: Chen X]]
-[[Category: Zhang, Y]]
+[[Category: Mclean LR]]
-[[Category: Nuclear protein]]
+[[Category: Zhang Y]]
-[[Category: Pxr]]