3an4: Difference between revisions
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<StructureSection load='3an4' size='340' side='right'caption='[[3an4]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='3an4' size='340' side='right'caption='[[3an4]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3an4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3an4]] 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=3AN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AN4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M7R:(2R)-2-BENZYL-3-(4-PROPOXY-3-{[({4-[(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DEC-1-YL]PHENYL}CARBONYL)AMINO]METHYL}PHENYL)PROPANOIC+ACID'>M7R</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M7R:(2R)-2-BENZYL-3-(4-PROPOXY-3-{[({4-[(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DEC-1-YL]PHENYL}CARBONYL)AMINO]METHYL}PHENYL)PROPANOIC+ACID'>M7R</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=3an4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3an4 OCA], [https://pdbe.org/3an4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3an4 RCSB], [https://www.ebi.ac.uk/pdbsum/3an4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3an4 ProSAT]</span></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=3an4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3an4 OCA], [https://pdbe.org/3an4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3an4 RCSB], [https://www.ebi.ac.uk/pdbsum/3an4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3an4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Miyachi | [[Category: Miyachi H]] | ||
[[Category: Morikawa | [[Category: Morikawa K]] | ||
[[Category: Ohashi | [[Category: Ohashi M]] | ||
[[Category: Oyama | [[Category: Oyama T]] | ||
[[Category: Waku | [[Category: Waku T]] | ||
Latest revision as of 18:49, 4 October 2023
Human PPAR gamma ligand binding domain in complex with a gamma selective agonist MO4RHuman PPAR gamma ligand binding domain in complex with a gamma selective agonist MO4R
Structural highlights
DiseasePPARG_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. FunctionPPARG_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 PubMedPeroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARgamma ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and computational studies of alpha-benzylphenylpropanoic acid PPARgamma agonists. Interestingly, these compounds show a reversal of the stereochemistry-transactivation activity relationship observed with other phenylpropanoic acid ligands. Design, Synthesis, and Structural Analysis of Phenylpropanoic Acid-Type PPARgamma-Selective Agonists: Discovery of Reversed Stereochemistry-Activity Relationship.,Ohashi M, Oyama T, Nakagome I, Satoh M, Nishio Y, Nobusada H, Hirono S, Morikawa K, Hashimoto Y, Miyachi H J Med Chem. 2010 Dec 3. PMID:21128600[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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