View source for 3fei


==Design and biological evaluation of novel, balanced dual PPARa/g agonists==
<StructureSection load='3fei' size='340' side='right'caption='[[3fei]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3fei]] 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=3FEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FEI 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTM:(2S)-3-(4-{[2-(4-CHLOROPHENYL)-1,3-THIAZOL-4-YL]METHOXY}-2-METHYLPHENYL)-2-ETHOXYPROPANOIC+ACID'>CTM</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=3fei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fei OCA], [https://pdbe.org/3fei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fei RCSB], [https://www.ebi.ac.uk/pdbsum/3fei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fei ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PPARA_HUMAN PPARA_HUMAN] Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.<ref>PMID:7684926</ref> <ref>PMID:7629123</ref> <ref>PMID:9556573</ref> <ref>PMID:10195690</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/fe/3fei_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=3fei ConSurf].
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== Publication Abstract from PubMed ==
An X-ray-guided design approach led to the identification of a novel, balanced class of alpha-ethoxy-phenylpropionic acid-derived dual PPARalpha/gamma agonists. The series shows a wide range of PPARalpha/gamma ratios within a rather narrow structural space. Advanced compounds possess favorable physicochemical and pharmacokinetic profiles and show a high efficacy in T2D and dyslipidemia animal models.

Design and biological evaluation of novel, balanced dual PPARalpha/gamma agonists.,Grether U, Benardeau A, Benz J, Binggeli A, Blum D, Hilpert H, Kuhn B, Marki HP, Meyer M, Mohr P, Puntener K, Raab S, Ruf A, Schlatter D ChemMedChem. 2009 Jun;4(6):951-6. PMID:19326383<ref>PMID:19326383</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3fei" 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: Large Structures]]
[[Category: Benz J]]
[[Category: Binggeli A]]
[[Category: Grether U]]
[[Category: Gsell B]]
[[Category: Hilpert H]]
[[Category: Maerki HP]]
[[Category: Mohr P]]
[[Category: Ruf A]]
[[Category: Schlatter D]]
[[Category: Stihle M]]