1i7i

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:23, 9 August 2023) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_1i7i| PDB=1i7i | SCENE= }}
 
-
===CRYSTAL STRUCTURE OF THE LIGAND BINDING DOMAIN OF HUMAN PPAR-GAMMA IN COMPLEX WITH THE AGONIST AZ 242===
 
-
{{ABSTRACT_PUBMED_11587644}}
 
-
==Function==
+
==CRYSTAL STRUCTURE OF THE LIGAND BINDING DOMAIN OF HUMAN PPAR-GAMMA IN COMPLEX WITH THE AGONIST AZ 242==
-
[[http://www.uniprot.org/uniprot/PPAT_HUMAN PPAT_HUMAN]] Dephosphorylates receptor tyrosine-protein kinase erbB-4 and inhibits the ligand-induced proteolytic cleavage.<ref>PMID:15219672</ref>
+
<StructureSection load='1i7i' size='340' side='right'caption='[[1i7i]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1i7i]] 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=1I7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I7I 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]] 2.35&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZ2:(2S)-2-ETHOXY-3-[4-(2-{4-[(METHYLSULFONYL)OXY]PHENYL}ETHOXY)PHENYL]PROPANOIC+ACID'>AZ2</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=1i7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i7i OCA], [https://pdbe.org/1i7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i7i RCSB], [https://www.ebi.ac.uk/pdbsum/1i7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i7i 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/i7/1i7i_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=1i7i ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
BACKGROUND: The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear receptor family. The roles of PPARalpha in fatty acid oxidation and PPARgamma in adipocyte differentiation and lipid storage have been characterized extensively. PPARs are activated by fatty acids and eicosanoids and are also targets for antidyslipidemic drugs, but the molecular interactions governing ligand selectivity for specific subtypes are unclear due to the lack of a PPARalpha ligand binding domain structure. RESULTS: We have solved the crystal structure of the PPARalpha ligand binding domain (LBD) in complex with the combined PPARalpha and -gamma agonist AZ 242, a novel dihydro cinnamate derivative that is structurally different from thiazolidinediones. In addition, we present the crystal structure of the PPARgamma_LBD/AZ 242 complex and provide a rationale for ligand selectivity toward the PPARalpha and -gamma subtypes. Heteronuclear NMR data on PPARalpha in both the apo form and in complex with AZ 242 shows an overall stabilization of the LBD upon agonist binding. A comparison of the novel PPARalpha/AZ 242 complex with the PPARgamma/AZ 242 complex and previously solved PPARgamma structures reveals a conserved hydrogen bonding network between agonists and the AF2 helix. CONCLUSIONS: The complex of PPARalpha and PPARgamma with the dual specificity agonist AZ 242 highlights the conserved interactions required for receptor activation. Together with the NMR data, this suggests a general model for ligand activation in the PPAR family. A comparison of the ligand binding sites reveals a molecular explanation for subtype selectivity and provides a basis for rational drug design.
-
==About this Structure==
+
Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family.,Cronet P, Petersen JF, Folmer R, Blomberg N, Sjoblom K, Karlsson U, Lindstedt EL, Bamberg K Structure. 2001 Aug;9(8):699-706. PMID:11587644<ref>PMID:11587644</ref>
-
[[1i7i]] is a 2 chain structure 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=1I7I OCA].
+
-
==See Also==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]]
+
</div>
 +
<div class="pdbe-citations 1i7i" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
<ref group="xtra">PMID:011587644</ref><references group="xtra"/><references/>
+
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Bamberg, K.]]
+
[[Category: Large Structures]]
-
[[Category: Blomberg, N.]]
+
[[Category: Bamberg K]]
-
[[Category: Cronet, P.]]
+
[[Category: Blomberg N]]
-
[[Category: Folmer, R.]]
+
[[Category: Cronet P]]
-
[[Category: Karlsson, U.]]
+
[[Category: Folmer R]]
-
[[Category: Lindstedt, E L.]]
+
[[Category: Karlsson U]]
-
[[Category: Petersen, J F.W.]]
+
[[Category: Lindstedt E-L]]
-
[[Category: Sjoblom, K.]]
+
[[Category: Petersen JFW]]
-
[[Category: Anti parallel helix sandwich]]
+
[[Category: Sjoblom K]]
-
[[Category: Transcription]]
+

Current revision

CRYSTAL STRUCTURE OF THE LIGAND BINDING DOMAIN OF HUMAN PPAR-GAMMA IN COMPLEX WITH THE AGONIST AZ 242

PDB ID 1i7i

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1i7i"
Personal tools