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3et2

From Proteopedia

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Current revision

Structure of PPARdelta with 3-[5-Methoxy-1-(4-methoxy-benzenesulfonyl)-1H-indol-3-yl]-propionic acid

Structural highlights

3et2 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.
Method:	X-ray diffraction, Resolution 2.24Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PPARD_HUMAN Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.^[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 PubMed

In a search for more effective anti-diabetic treatment, we used a process coupling low-affinity biochemical screening with high-throughput co-crystallography in the design of a series of compounds that selectively modulate the activities of all three peroxisome proliferator-activated receptors (PPARs), PPARalpha, PPARgamma, and PPARdelta. Transcriptional transactivation assays were used to select compounds from this chemical series with a bias toward partial agonism toward PPARgamma, to circumvent the clinically observed side effects of full PPARgamma agonists. Co-crystallographic characterization of the lead molecule, indeglitazar, in complex with each of the 3 PPARs revealed the structural basis for its PPAR pan-activity and its partial agonistic response toward PPARgamma. Compared with full PPARgamma-agonists, indeglitazar is less potent in promoting adipocyte differentiation and only partially effective in stimulating adiponectin gene expression. Evaluation of the compound in vivo confirmed the reduced adiponectin response in animal models of obesity and diabetes while revealing strong beneficial effects on glucose, triglycerides, cholesterol, body weight, and other metabolic parameters. Indeglitazar has now progressed to Phase II clinical evaluations for Type 2 diabetes mellitus (T2DM).

Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent.,Artis DR, Lin JJ, Zhang C, Wang W, Mehra U, Perreault M, Erbe D, Krupka HI, England BP, Arnold J, Plotnikov AN, Marimuthu A, Nguyen H, Will S, Signaevsky M, Kral J, Cantwell J, Settachatgull C, Yan DS, Fong D, Oh A, Shi S, Womack P, Powell B, Habets G, West BL, Zhang KY, Milburn MV, Vlasuk GP, Hirth KP, Nolop K, Bollag G, Ibrahim PN, Tobin JF Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7. Epub 2008 Dec 30. PMID:19116277^[3]

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

References

↑ Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol. 1992 Oct;6(10):1634-41. PMID:1333051 doi:http://dx.doi.org/10.1210/mend.6.10.1333051
↑ van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005 Mar;46(3):526-34. Epub 2004 Dec 16. PMID:15604518 doi:http://dx.doi.org/10.1194/jlr.M400400-JLR200
↑ Artis DR, Lin JJ, Zhang C, Wang W, Mehra U, Perreault M, Erbe D, Krupka HI, England BP, Arnold J, Plotnikov AN, Marimuthu A, Nguyen H, Will S, Signaevsky M, Kral J, Cantwell J, Settachatgull C, Yan DS, Fong D, Oh A, Shi S, Womack P, Powell B, Habets G, West BL, Zhang KY, Milburn MV, Vlasuk GP, Hirth KP, Nolop K, Bollag G, Ibrahim PN, Tobin JF. Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7. Epub 2008 Dec 30. PMID:19116277

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3et2"

Categories: Homo sapiens | Large Structures | Wang W | Zhang KYJ

@@ Line 3: / Line 3: @@
 <StructureSection load='3et2' size='340' side='right'caption='[[3et2]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3et2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ET2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ET2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3et2]] 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=3ET2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ET2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BO:1-BUTANOL'>1BO</scene>, <scene name='pdbligand=ET1:3-{5-METHOXY-1-[(4-METHOXYPHENYL)SULFONYL]-1H-INDOL-3-YL}PROPANOIC+ACID'>ET1</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3et0|3et0]], [[3et1|3et1]], [[3et3|3et3]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BO:1-BUTANOL'>1BO</scene>, <scene name='pdbligand=ET1:3-{5-METHOXY-1-[(4-METHOXYPHENYL)SULFONYL]-1H-INDOL-3-YL}PROPANOIC+ACID'>ET1</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPARD, NR1C2, PPARB ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3et2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3et2 OCA], [https://pdbe.org/3et2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3et2 RCSB], [https://www.ebi.ac.uk/pdbsum/3et2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3et2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/PPARD_HUMAN PPARD_HUMAN]] Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.<ref>PMID:1333051</ref> <ref>PMID:15604518</ref>
+[https://www.uniprot.org/uniprot/PPARD_HUMAN PPARD_HUMAN] Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.<ref>PMID:1333051</ref> <ref>PMID:15604518</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Wang, W]]
+[[Category: Wang W]]
-[[Category: Zhang, K Y.J]]
+[[Category: Zhang KYJ]]
-[[Category: Activator]]
-[[Category: Adiponectin]]
-[[Category: Alternative splicing]]
-[[Category: Diabetes]]
-[[Category: Dna-binding]]
-[[Category: Drug discovery]]
-[[Category: Fragment-based drug discovery]]
-[[Category: K zhang]]
-[[Category: Metabolic disease]]
-[[Category: Metal-binding]]
-[[Category: Nucleus]]
-[[Category: Ppar]]
-[[Category: Ppard]]
-[[Category: Ppardelta]]
-[[Category: Receptor]]
-[[Category: Scaffold-based drug discovery]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Wed oct 1 17:27:09 2008 on nod]]
-[[Category: Zinc]]
-[[Category: Zinc-finger]]

3et2

From Proteopedia

Current revision

Structure of PPARdelta with 3-[5-Methoxy-1-(4-methoxy-benzenesulfonyl)-1H-indol-3-yl]-propionic acid

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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