4a4w
From Proteopedia
(Difference between revisions)
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| - | {{STRUCTURE_4a4w| PDB=4a4w | SCENE= }} | ||
| - | ===Ligand binding domain of human PPAR gamma in complex with amorfrutin B=== | ||
| - | {{ABSTRACT_PUBMED_23286787}} | ||
| - | ==Disease== | + | ==Ligand binding domain of human PPAR gamma in complex with amorfrutin B== |
| + | <StructureSection load='4a4w' size='340' side='right' caption='[[4a4w]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4a4w]] 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=4A4W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A4W FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YFB:AMORFRUTIN+B'>YFB</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fvj|2fvj]], [[2xkw|2xkw]], [[2vv2|2vv2]], [[1fm9|1fm9]], [[2vv0|2vv0]], [[2vv1|2vv1]], [[2prg|2prg]], [[1knu|1knu]], [[1rdt|1rdt]], [[2vv4|2vv4]], [[3prg|3prg]], [[1i7i|1i7i]], [[1k74|1k74]], [[1fm6|1fm6]], [[1prg|1prg]], [[1zgy|1zgy]], [[2f4b|2f4b]], [[2vst|2vst]], [[2g0h|2g0h]], [[2vsr|2vsr]], [[1wm0|1wm0]], [[4prg|4prg]], [[2g0g|2g0g]], [[1nyx|1nyx]], [[2vv3|2vv3]], [[2yfe|2yfe]], [[4a4v|4a4v]]</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=4a4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a4w OCA], [http://pdbe.org/4a4w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a4w RCSB], [http://www.ebi.ac.uk/pdbsum/4a4w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a4w ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://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:[http://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:[http://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:[http://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. | [[http://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:[http://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:[http://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:[http://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 == | |
| - | ==Function== | + | |
[[http://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> | [[http://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Amorfrutins are a family of natural products with high affinity to the peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor regulating lipid and glucose metabolism. The PPARgamma agonist rosiglitazone increases insulin sensitivity and is effective against type II diabetes but has severe adverse effects including weight gain. Amorfrutins improve insulin sensitivity and dyslipidemia but do not enhance undesired fat storage. They bear potential as therapeutics or prophylactic dietary supplements. We identified amorfrutin B as a novel partial agonist of PPARgamma with a considerably higher affinity than that of previously reported amorfrutins, similar to that of rosiglitazone. Crystal structures reveal the geranyl side chain of amorfrutin B as the cause of its particularly high affinity. Typical for partial agonists, amorfrutins 1, 2, and B bind helix H3 and the beta-sheet of PPARgamma but not helix H12. | ||
| + | |||
| + | Structural characterization of amorfrutins bound to the peroxisome proliferator-activated receptor gamma.,de Groot JC, Weidner C, Krausze J, Kawamoto K, Schroeder FC, Sauer S, Bussow K J Med Chem. 2013 Feb 28;56(4):1535-43. doi: 10.1021/jm3013272. Epub 2013 Feb 6. PMID:23286787<ref>PMID:23286787</ref> | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 4a4w" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | + | *[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| - | [[Category: Buessow, K | + | [[Category: Buessow, K]] |
| - | [[Category: Groot, J C.de | + | [[Category: Groot, J C.de]] |
| - | [[Category: Kawamoto, K | + | [[Category: Kawamoto, K]] |
| - | [[Category: Krausze, J | + | [[Category: Krausze, J]] |
| - | [[Category: Sauer, S | + | [[Category: Sauer, S]] |
| - | [[Category: Schroeder, F C | + | [[Category: Schroeder, F C]] |
| - | [[Category: Weidner, C | + | [[Category: Weidner, C]] |
[[Category: Agonist]] | [[Category: Agonist]] | ||
[[Category: Diabetes]] | [[Category: Diabetes]] | ||
[[Category: Insulin resistance]] | [[Category: Insulin resistance]] | ||
[[Category: Receptor]] | [[Category: Receptor]] | ||
Revision as of 11:29, 4 August 2016
Ligand binding domain of human PPAR gamma in complex with amorfrutin B
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Categories: Human | Buessow, K | Groot, J C.de | Kawamoto, K | Krausze, J | Sauer, S | Schroeder, F C | Weidner, C | Agonist | Diabetes | Insulin resistance | Receptor
