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2yfe

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Revision as of 19:11, 4 August 2016

Ligand binding domain of human PPAR gamma in complex with amorfrutin 1

Structural highlights

2yfe is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2fvj, 2vv2, 1fm9, 2xkw, 2vv0, 2vv1, 2prg, 1knu, 1rdt, 2vv4, 3prg, 1i7i, 1k74, 1fm6, 1zgy, 1prg, 2f4b, 2vst, 2g0h, 2vsr, 1wm0, 4prg, 1nyx, 2vv3, 2g0g
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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: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.^[1] Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM: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.^[2] ^[3] Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM: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

[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.^[4] ^[5] ^[6]

Publication Abstract from PubMed

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARgamma-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARgamma, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARgamma drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARgamma-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.

Amorfrutins are potent antidiabetic dietary natural products.,Weidner C, de Groot JC, Prasad A, Freiwald A, Quedenau C, Kliem M, Witzke A, Kodelja V, Han CT, Giegold S, Baumann M, Klebl B, Siems K, Muller-Kuhrt L, Schurmann A, Schuler R, Pfeiffer AF, Schroeder FC, Bussow K, Sauer S Proc Natl Acad Sci U S A. 2012 Apr 16. PMID:22509006^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med. 1998 Oct 1;339(14):953-9. PMID:9753710 doi:10.1056/NEJM199810013391403
↑ Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T. PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes. 2002 Dec;51(12):3586-90. PMID:12453919
↑ Agarwal AK, Garg A. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002 Jan;87(1):408-11. PMID:11788685
↑ Mukherjee R, Jow L, Croston GE, Paterniti JR Jr. Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists. J Biol Chem. 1997 Mar 21;272(12):8071-6. PMID:9065481
↑ Yin Y, Yuan H, Wang C, Pattabiraman N, Rao M, Pestell RG, Glazer RI. 3-phosphoinositide-dependent protein kinase-1 activates the peroxisome proliferator-activated receptor-gamma and promotes adipocyte differentiation. Mol Endocrinol. 2006 Feb;20(2):268-78. Epub 2005 Sep 8. PMID:16150867 doi:10.1210/me.2005-0197
↑ Park SH, Choi HJ, Yang H, Do KH, Kim J, Lee DW, Moon Y. Endoplasmic reticulum stress-activated C/EBP homologous protein enhances nuclear factor-kappaB signals via repression of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2010 Nov 12;285(46):35330-9. doi: 10.1074/jbc.M110.136259. Epub 2010, Sep 9. PMID:20829347 doi:10.1074/jbc.M110.136259
↑ Weidner C, de Groot JC, Prasad A, Freiwald A, Quedenau C, Kliem M, Witzke A, Kodelja V, Han CT, Giegold S, Baumann M, Klebl B, Siems K, Muller-Kuhrt L, Schurmann A, Schuler R, Pfeiffer AF, Schroeder FC, Bussow K, Sauer S. Amorfrutins are potent antidiabetic dietary natural products. Proc Natl Acad Sci U S A. 2012 Apr 16. PMID:22509006 doi:10.1073/pnas.1116971109

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2yfe"

@@ Line 1: / Line 1: @@
 ==Ligand binding domain of human PPAR gamma in complex with amorfrutin 1==
 <StructureSection load='2yfe' size='340' side='right' caption='[[2yfe]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2yfe]] 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=2YFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YFE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2yfe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YFE FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YFE:AMORFRUTIN+1'>YFE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fvj|2fvj]], [[2vv2|2vv2]], [[1fm9|1fm9]], [[2xkw|2xkw]], [[2vv0|2vv0]], [[2vv1|2vv1]], [[2prg|2prg]], [[1knu|1knu]], [[1rdt|1rdt]], [[2vv4|2vv4]], [[3prg|3prg]], [[1i7i|1i7i]], [[1k74|1k74]], [[1fm6|1fm6]], [[1zgy|1zgy]], [[1prg|1prg]], [[2f4b|2f4b]], [[2vst|2vst]], [[2g0h|2g0h]], [[2vsr|2vsr]], [[1wm0|1wm0]], [[4prg|4prg]], [[1nyx|1nyx]], [[2vv3|2vv3]], [[2g0g|2g0g]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yfe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yfe RCSB], [http://www.ebi.ac.uk/pdbsum/2yfe PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yfe OCA], [http://pdbe.org/2yfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yfe RCSB], [http://www.ebi.ac.uk/pdbsum/2yfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yfe ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2yfe" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Buessow, K]]
 [[Category: Groot, J C.De]]

2yfe

From Proteopedia

Revision as of 19:11, 4 August 2016

Ligand binding domain of human PPAR gamma in complex with amorfrutin 1

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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