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==PPARgamma in complex with a 2-BABA compound== | |||
=== | <StructureSection load='1wm0' size='340' side='right' caption='[[1wm0]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1wm0]] 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=1WM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WM0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLB:2-[(2,4-DICHLOROBENZOYL)AMINO]-5-(PYRIMIDIN-2-YLOXY)BENZOIC+ACID'>PLB</scene></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=1wm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wm0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wm0 RCSB], [http://www.ebi.ac.uk/pdbsum/1wm0 PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/NCOA2_MOUSE NCOA2_MOUSE]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:12507421</ref> <ref>PMID:11997499</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/wm/1wm0_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the NR1 subfamily of nuclear receptors. The PPARs play key roles in the control of glucose and lipid homeostasis, and the synthetic isoform-specific PPAR agonists are used clinically to improve insulin sensitivity and to lower serum triglyceride levels. All of the previously reported PPAR agonists form the same characteristic interactions with the receptor, which have been postulated to be important for the induction of agonistic activity. Here we describe a new class of PPARalpha/gamma modulators, the 5-substituted 2-benzoylaminobenzoic acids (2-BABAs). As shown by x-ray crystallography, the representative compounds BVT.13, BVT.762, and BVT.763, utilize a novel binding epitope and lack the agonist-characteristic interactions. Despite this, some compounds within the 2-BABA family are potent agonists in a cell-based reporter gene assay. Furthermore, BVT.13 displays antidiabetic effects in ob/ob mice. We concluded that the 2-BABA binding mode can be used to design isoform-specific PPAR modulators with biological activity in vivo. | |||
A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects.,Ostberg T, Svensson S, Selen G, Uppenberg J, Thor M, Sundbom M, Sydow-Backman M, Gustavsson AL, Jendeberg L J Biol Chem. 2004 Sep 24;279(39):41124-30. Epub 2004 Jul 15. PMID:15258145<ref>PMID:15258145</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]] | *[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Gustavsson, A L | [[Category: Gustavsson, A L]] | ||
[[Category: Jendeberg, L | [[Category: Jendeberg, L]] | ||
[[Category: Ostberg, T | [[Category: Ostberg, T]] | ||
[[Category: Selen, G | [[Category: Selen, G]] | ||
[[Category: Sundbom, M | [[Category: Sundbom, M]] | ||
[[Category: Svensson, S | [[Category: Svensson, S]] | ||
[[Category: Sydow-Backman, M | [[Category: Sydow-Backman, M]] | ||
[[Category: Thor, M | [[Category: Thor, M]] | ||
[[Category: Uppenberg, J | [[Category: Uppenberg, J]] | ||
[[Category: Three-layer helical domain]] | [[Category: Three-layer helical domain]] | ||
[[Category: Transcription-signaling protein complex]] | [[Category: Transcription-signaling protein complex]] | ||
Revision as of 08:31, 25 December 2014
PPARgamma in complex with a 2-BABA compoundPPARgamma in complex with a 2-BABA compound
Structural highlights
Function[NCOA2_MOUSE] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the NR1 subfamily of nuclear receptors. The PPARs play key roles in the control of glucose and lipid homeostasis, and the synthetic isoform-specific PPAR agonists are used clinically to improve insulin sensitivity and to lower serum triglyceride levels. All of the previously reported PPAR agonists form the same characteristic interactions with the receptor, which have been postulated to be important for the induction of agonistic activity. Here we describe a new class of PPARalpha/gamma modulators, the 5-substituted 2-benzoylaminobenzoic acids (2-BABAs). As shown by x-ray crystallography, the representative compounds BVT.13, BVT.762, and BVT.763, utilize a novel binding epitope and lack the agonist-characteristic interactions. Despite this, some compounds within the 2-BABA family are potent agonists in a cell-based reporter gene assay. Furthermore, BVT.13 displays antidiabetic effects in ob/ob mice. We concluded that the 2-BABA binding mode can be used to design isoform-specific PPAR modulators with biological activity in vivo. A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects.,Ostberg T, Svensson S, Selen G, Uppenberg J, Thor M, Sundbom M, Sydow-Backman M, Gustavsson AL, Jendeberg L J Biol Chem. 2004 Sep 24;279(39):41124-30. Epub 2004 Jul 15. PMID:15258145[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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