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{{STRUCTURE_1knu|  PDB=1knu  |  SCENE=  }}
==LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST==
===LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST===
<StructureSection load='1knu' size='340' side='right' caption='[[1knu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
{{ABSTRACT_PUBMED_11831892}}
== Structural highlights ==
<table><tr><td colspan='2'>[[1knu]] 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=1KNU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KNU FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YPA:(S)-3-(4-(2-CARBAZOL-9-YL-ETHOXY)-PHENYL)-2-ETHOXY-PROPIONIC+ACID'>YPA</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1prg|1prg]], [[2prg|2prg]]</td></tr>
<tr><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 Homo sapiens])</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1knu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1knu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1knu RCSB], [http://www.ebi.ac.uk/pdbsum/1knu PDBsum]</span></td></tr>
<table>
== 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/kn/1knu_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 ==
Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.


==Function==
Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity.,Sauerberg P, Pettersson I, Jeppesen L, Bury PS, Mogensen JP, Wassermann K, Brand CL, Sturis J, Woldike HF, Fleckner J, Andersen AS, Mortensen SB, Svensson LA, Rasmussen HB, Lehmann SV, Polivka Z, Sindelar K, Panajotova V, Ynddal L, Wulff EM J Med Chem. 2002 Feb 14;45(4):789-804. PMID:11831892<ref>PMID:11831892</ref>
[[http://www.uniprot.org/uniprot/PPAT_HUMAN PPAT_HUMAN]] Dephosphorylates receptor tyrosine-protein kinase erbB-4 and inhibits the ligand-induced proteolytic cleavage.<ref>PMID:15219672</ref>  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[1knu]] 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=1KNU OCA].
</div>


==See Also==
==See Also==
*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]]
*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:011831892</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Fleckner, J.]]
[[Category: Fleckner, J.]]

Revision as of 20:29, 29 September 2014

LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONISTLIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST

Structural highlights

1knu is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:1prg, 2prg
Gene:PPARG, NR1C3 (Homo sapiens)
Resources:FirstGlance, OCA, RCSB, PDBsum

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 PubMed

Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.

Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity.,Sauerberg P, Pettersson I, Jeppesen L, Bury PS, Mogensen JP, Wassermann K, Brand CL, Sturis J, Woldike HF, Fleckner J, Andersen AS, Mortensen SB, Svensson LA, Rasmussen HB, Lehmann SV, Polivka Z, Sindelar K, Panajotova V, Ynddal L, Wulff EM J Med Chem. 2002 Feb 14;45(4):789-804. PMID:11831892[1]

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

See Also

References

  1. ↑ Sauerberg P, Pettersson I, Jeppesen L, Bury PS, Mogensen JP, Wassermann K, Brand CL, Sturis J, Woldike HF, Fleckner J, Andersen AS, Mortensen SB, Svensson LA, Rasmussen HB, Lehmann SV, Polivka Z, Sindelar K, Panajotova V, Ynddal L, Wulff EM. Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity. J Med Chem. 2002 Feb 14;45(4):789-804. PMID:11831892

1knu, resolution 2.50Å

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