3fej: Difference between revisions

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-[[Image:3fej.png|left|200px]]
-<!--
+==Design and biological evaluation of novel, balanced dual PPARa/g agonists==
-The line below this paragraph, containing "STRUCTURE_3fej", creates the "Structure Box" on the page.
+<StructureSection load='3fej' size='340' side='right'caption='[[3fej]], [[Resolution|resolution]] 2.01&Aring;' 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'>[[3fej]] 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=3FEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FEJ 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]] 2.01&#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>
-{{STRUCTURE_3fej|  PDB=3fej  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3fej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fej OCA], [https://pdbe.org/3fej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fej RCSB], [https://www.ebi.ac.uk/pdbsum/3fej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fej ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer.  Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref>   Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[https://omim.org/entry/604367 604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref>   Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
+== Function ==
+[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</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/3fej_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=3fej ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== 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 PPARa/g agonists===
+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>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_19326383}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 3fej" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 19326383 is the PubMed ID number.
--->
-{{ABSTRACT_PUBMED_19326383}}
-==About this Structure==
-[[3fej]] is a 2 chain structure of [[Peroxisome Proliferator-Activated Receptors]] 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=3FEJ OCA].
 ==See Also==
-*[[Peroxisome Proliferator-Activated Receptors]]
+*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:19326383</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Benz, J.]]
+[[Category: Large Structures]]
-[[Category: Binggeli, A.]]
+[[Category: Benz J]]
-[[Category: Grether, U.]]
+[[Category: Binggeli A]]
-[[Category: Gsell, B.]]
+[[Category: Grether U]]
-[[Category: Hilpert, H.]]
+[[Category: Gsell B]]
-[[Category: Kuhn, B.]]
+[[Category: Hilpert H]]
-[[Category: Maerki, H P.]]
+[[Category: Kuhn B]]
-[[Category: Mohr, P.]]
+[[Category: Maerki HP]]
-[[Category: Ruf, A.]]
+[[Category: Mohr P]]
-[[Category: Stihle, M.]]
+[[Category: Ruf A]]
-[[Category: Activator]]
+[[Category: Stihle M]]
-[[Category: Alternative splicing]]
-[[Category: Diabetes]]
-[[Category: Diabetes mellitus]]
-[[Category: Disease mutation]]
-[[Category: Dna-binding]]
-[[Category: Metal-binding]]
-[[Category: Nuclear recpetor]]
-[[Category: Nucleus]]
-[[Category: Obesity]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Receptor]]
-[[Category: Transcription]]
-[[Category: Transcription factor]]
-[[Category: Transcription regulation]]
-[[Category: Zinc]]
-[[Category: Zinc-finger]]