2zvt: Difference between revisions

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-[[Image:2zvt.png|left|200px]]
-<!--
+==Cys285Ser mutant PPARgamma ligand-binding domain complexed with 15-deoxy-delta12,14-prostaglandin J2==
-The line below this paragraph, containing "STRUCTURE_2zvt", creates the "Structure Box" on the page.
+<StructureSection load='2zvt' size='340' side='right'caption='[[2zvt]], [[Resolution|resolution]] 1.90&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'>[[2zvt]] 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=2ZVT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZVT 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]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTG:(5E,14E)-11-OXOPROSTA-5,9,12,14-TETRAEN-1-OIC+ACID'>PTG</scene></td></tr>
-{{STRUCTURE_2zvt|  PDB=2zvt  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2zvt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zvt OCA], [https://pdbe.org/2zvt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zvt RCSB], [https://www.ebi.ac.uk/pdbsum/2zvt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zvt 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/zv/2zvt_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=2zvt ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) activates a nuclear receptor heterodimer, peroxisome proliferators-activated receptor gamma (PPARgamma)/ retinoid X receptor (RXRalpha) through covalent binding to Cys285 in PPARgamma ligand-binding domain (LBD). Here, we present the 1.9A crystal structure of C285S mutant LBD complexed with 15d-PGJ(2), corresponding to the non-covalently bound state. The ligand lies adjacent to a hydrogen-bond network around the helix H2 and the nearby beta-sheet. Comparisons with previous structures clarified the relationships between PPARgamma function and conformational alterations of LBD during the process of covalently binding ligands, such as 15d-PGJ(2), and thus suggested a mechanism, by which these ligands modulate PPARgamma/RXRalpha function through conformational changes of the loop following helix H2' and the beta-sheet.
-===Cys285Ser mutant PPARgamma ligand-binding domain complexed with 15-deoxy-delta12,14-prostaglandin J2===
+Atomic structure of mutant PPARgamma LBD complexed with 15d-PGJ2: novel modulation mechanism of PPARgamma/RXRalpha function by covalently bound ligands.,Waku T, Shiraki T, Oyama T, Morikawa K FEBS Lett. 2009 Jan 22;583(2):320-4. Epub 2008 Dec 26. PMID:19101554<ref>PMID:19101554</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_19101554}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 2zvt" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 19101554 is the PubMed ID number.
--->
-{{ABSTRACT_PUBMED_19101554}}
-==About this Structure==
-[[2zvt]] 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=2ZVT 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:19101554</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Morikawa, K.]]
+[[Category: Large Structures]]
-[[Category: Oyama, T.]]
+[[Category: Morikawa K]]
-[[Category: Shiraki, T.]]
+[[Category: Oyama T]]
-[[Category: Waku, T.]]
+[[Category: Shiraki T]]
-[[Category: Activator]]
+[[Category: Waku T]]
-[[Category: Alternative splicing]]
-[[Category: Anti parallel helix sandwich]]
-[[Category: Diabetes mellitus]]
-[[Category: Disease mutation]]
-[[Category: Dna-binding]]
-[[Category: Metal-binding]]
-[[Category: Nucleus]]
-[[Category: Obesity]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Receptor]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Zinc]]
-[[Category: Zinc-finger]]