2j14: Difference between revisions
New page: left|200px<br /> <applet load="2j14" size="450" color="white" frame="true" align="right" spinBox="true" caption="2j14, resolution 2.80Å" /> '''3,4,5-TRISUBSTITUTE... |
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== | ==3,4,5-Trisubstituted Isoxazoles as Novel PPARdelta Agonists: Part2== | ||
A series of PPARdelta-selective agonists was investigated and optimized | <StructureSection load='2j14' size='340' side='right'caption='[[2j14]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2j14]] 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=2J14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J14 FirstGlance]. <br> | |||
</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=GNI:(3-{4-[2-(2,4-DICHLORO-PHENOXY)-ETHYLCARBAMOYL]-5-PHENYL-ISOXAZOL-3-YL}-PHENYL)-ACETIC+ACID'>GNI</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=2j14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j14 OCA], [https://pdbe.org/2j14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j14 RCSB], [https://www.ebi.ac.uk/pdbsum/2j14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j14 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PPARD_HUMAN PPARD_HUMAN] Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.<ref>PMID:1333051</ref> <ref>PMID:15604518</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j1/2j14_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2j14 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of PPARdelta-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARdelta agonist with good in vivo PK properties in mouse (C(max)=5.1 microM, t(1/2)=3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARdelta is discussed. | |||
3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2.,Epple R, Azimioara M, Russo R, Xie Y, Wang X, Cow C, Wityak J, Karanewsky D, Bursulaya B, Kreusch A, Tuntland T, Gerken A, Iskandar M, Saez E, Martin Seidel H, Tian SS Bioorg Med Chem Lett. 2006 Nov 1;16(21):5488-92. Epub 2006 Aug 22. PMID:16931011<ref>PMID:16931011</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 2j14" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Azimioara | [[Category: Azimioara M]] | ||
[[Category: Bursulaya | [[Category: Bursulaya B]] | ||
[[Category: Cow | [[Category: Cow C]] | ||
[[Category: Epple | [[Category: Epple R]] | ||
[[Category: Gerken | [[Category: Gerken A]] | ||
[[Category: Iskandar | [[Category: Iskandar M]] | ||
[[Category: Karanewsky | [[Category: Karanewsky D]] | ||
[[Category: Kreusch | [[Category: Kreusch A]] | ||
[[Category: Russo | [[Category: Russo R]] | ||
[[Category: Saez | [[Category: Saez E]] | ||
[[Category: Seidel | [[Category: Seidel HM]] | ||
[[Category: Tian | [[Category: Tian SS]] | ||
[[Category: Tuntland | [[Category: Tuntland T]] | ||
[[Category: Wang | [[Category: Wang X]] | ||
[[Category: Wityak | [[Category: Wityak J]] | ||
[[Category: Xie | [[Category: Xie Y]] | ||
