6avi: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6avi' size='340' side='right' caption='[[6avi]], [[Resolution|resolution]] 2.29Å' scene=''> | <StructureSection load='6avi' size='340' side='right' caption='[[6avi]], [[Resolution|resolution]] 2.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6avi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AVI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVI FirstGlance]. <br> | <table><tr><td colspan='2'>[[6avi]] 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=6AVI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AVI FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GW9:2-CHLORO-5-NITRO-N-PHENYLBENZAMIDE'>GW9</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GW9:2-CHLORO-5-NITRO-N-PHENYLBENZAMIDE'>GW9</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6avi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avi OCA], [http://pdbe.org/6avi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avi RCSB], [http://www.ebi.ac.uk/pdbsum/6avi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avi ProSAT]</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=6avi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6avi OCA], [http://pdbe.org/6avi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6avi RCSB], [http://www.ebi.ac.uk/pdbsum/6avi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6avi ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 11: | Line 12: | ||
== 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 == | |||
Crystal structures of peroxisome proliferator-activated receptor gamma (PPARgamma) have revealed overlapping binding modes for synthetic and natural/endogenous ligands, indicating competition for the orthosteric pocket. Here we show that cobinding of a synthetic ligand to the orthosteric pocket can push natural and endogenous PPARgamma ligands (fatty acids) out of the orthosteric pocket towards an alternate ligand-binding site near the functionally important omega (Omega)-loop. X-ray crystallography, NMR spectroscopy, all-atom molecular dynamics simulations, and mutagenesis coupled to quantitative biochemical functional and cellular assays reveal that synthetic ligand and fatty acid cobinding can form a 'ligand link' to the Omega-loop and synergistically affect the structure and function of PPARgamma. These findings contribute to a growing body of evidence indicating ligand binding to nuclear receptors can be more complex than the classical one-for-one orthosteric exchange of a natural or endogenous ligand with a synthetic ligand. | |||
Cooperative cobinding of synthetic and natural ligands to the nuclear receptor PPARgamma.,Shang J, Brust R, Mosure SA, Bass J, Munoz-Tello P, Lin H, Hughes TS, Tang M, Ge Q, Kamenekca TM, Kojetin DJ Elife. 2018 Dec 21;7. pii: 43320. doi: 10.7554/eLife.43320. PMID:30575522<ref>PMID:30575522</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6avi" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Kojetin, D J]] | [[Category: Kojetin, D J]] | ||
[[Category: Shang, J]] | [[Category: Shang, J]] | ||