3ia6

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{{Seed}}
 
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[[Image:3ia6.png|left|200px]]
 
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==X-ray Crystal structure of the nuclear hormone receptor PPAR-gamma in a complex with a PPAR gamma/alpha dual agonist==
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The line below this paragraph, containing "STRUCTURE_3ia6", creates the "Structure Box" on the page.
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<StructureSection load='3ia6' size='340' side='right'caption='[[3ia6]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3ia6]] 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=3IA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IA6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNT:(2S)-3-{4-[3-(5-METHYL-2-PHENYL-1,3-OXAZOL-4-YL)PROPYL]PHENYL}-2-(2H-1,2,3-TRIAZOL-2-YL)PROPANOIC+ACID'>UNT</scene></td></tr>
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{{STRUCTURE_3ia6| PDB=3ia6 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ia6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ia6 OCA], [https://pdbe.org/3ia6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ia6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ia6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ia6 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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.
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ia/3ia6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3ia6 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The synthesis of a new series of phenylpropanoic acid derivatives incorporating an heteroaryl group at the alpha-position and their evaluation for binding and activation of PPARalpha and PPARgamma are presented in this report. Among the new compounds, (S)-3-{4-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-phenyl}-2-1,2,3-triazo l-2-yl-propionic acid (17j), was identified as a potent human PPARalpha/gamma dual agonist (EC(50)=0.013 and 0.061 microM, respectively) with demonstrated oral bioavailability in rat and dog. 17j was shown to decrease insulin levels, plasma glucose, and triglycerides in the ZDF female rat model. In the human apolipoprotein A-1/CETP transgenic mouse model 17j produced increases in hApoA1 and HDL-C and decreases in plasma triglycerides. The increased potency for binding and activation of both PPAR subtypes observed with 17j when compared to previous analogs in this series was explained based on results derived from crystallographic and modeling studies.
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===X-ray Crystal structure of the nuclear hormone receptor PPAR-gamma in a complex with a PPAR gamma/alpha dual agonist===
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Synthesis and evaluation of novel alpha-heteroaryl-phenylpropanoic acid derivatives as PPARalpha/gamma dual agonists.,Casimiro-Garcia A, Bigge CF, Davis JA, Padalino T, Pulaski J, Ohren JF, McConnell P, Kane CD, Royer LJ, Stevens KA, Auerbach B, Collard W, McGregor C, Song K Bioorg Med Chem. 2009 Oct 15;17(20):7113-25. Epub 2009 Sep 6. PMID:19783444<ref>PMID:19783444</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3ia6" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19783444}}, adds the Publication Abstract to the page
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*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19783444 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19783444}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3IA6 is a 2 chains structure with sequences 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=3IA6 OCA].
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==Reference==
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<ref group="xtra">PMID:19783444</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Ohren, J F.]]
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[[Category: Large Structures]]
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[[Category: Activator]]
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[[Category: Ohren JF]]
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[[Category: Alternative splicing]]
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[[Category: Diabetes mellitus]]
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[[Category: Disease mutation]]
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[[Category: Dna-binding]]
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[[Category: Dual specificity]]
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[[Category: Inhibitor]]
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[[Category: Metal-binding]]
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[[Category: Nucleus]]
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[[Category: Obesity]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Protein-ligand complex]]
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[[Category: Receptor]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Zinc]]
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[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 28 14:44:13 2010''
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Current revision

X-ray Crystal structure of the nuclear hormone receptor PPAR-gamma in a complex with a PPAR gamma/alpha dual agonist

PDB ID 3ia6

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