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5hyk

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Revision as of 08:36, 27 May 2020

Crystal structure of the complex PPARalpha/AL26-29

Structural highlights

5hyk is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	PPARA, NR1C1, PPAR (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PPARA_HUMAN] Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of the metabolic homeostasis and therefore represent valuable therapeutic targets for the treatment of metabolic diseases. The development of more balanced drugs interacting with PPARs, devoid of the side-effects showed by the currently marketed PPARgamma full agonists, is considered the major challenge for the pharmaceutical companies. Here we present a structure-based virtual screening approach that let us identify a novel PPAR pan-agonist with a very attractive activity profile and its crystal structure in the complex with PPARalpha and PPARgamma, respectively. In PPARalpha this ligand occupies a new pocket whose filling is allowed by the ligand-induced switching of the F273 side chain from a closed to an open conformation. The comparison between this pocket and the corresponding cavity in PPARgamma provides a rationale for the different activation of the ligand towards PPARalpha and PPARgamma, suggesting a novel basis for ligand design.

Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode.,Capelli D, Cerchia C, Montanari R, Loiodice F, Tortorella P, Laghezza A, Cervoni L, Pochetti G, Lavecchia A Sci Rep. 2016 Oct 6;6:34792. doi: 10.1038/srep34792. PMID:27708429^[5]

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

References

↑ Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry. 1993 Jun 1;32(21):5598-604. PMID:7684926
↑ Juge-Aubry CE, Gorla-Bajszczak A, Pernin A, Lemberger T, Wahli W, Burger AG, Meier CA. Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat. J Biol Chem. 1995 Jul 28;270(30):18117-22. PMID:7629123
↑ Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, Jetten AM. Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4. J Biol Chem. 1998 May 1;273(18):10948-57. PMID:9556573
↑ Gorla-Bajszczak A, Juge-Aubry C, Pernin A, Burger AG, Meier CA. Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):37-47. PMID:10195690
↑ Capelli D, Cerchia C, Montanari R, Loiodice F, Tortorella P, Laghezza A, Cervoni L, Pochetti G, Lavecchia A. Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode. Sci Rep. 2016 Oct 6;6:34792. doi: 10.1038/srep34792. PMID:27708429 doi:http://dx.doi.org/10.1038/srep34792

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5hyk"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the complex PPARalpha/AL26-29==
-<StructureSection load='5hyk' size='340' side='right' caption='[[5hyk]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
+<StructureSection load='5hyk' size='340' side='right'caption='[[5hyk]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hyk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HYK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hyk]] is a 1 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=5HYK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HYK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=65W:2-METHYL-2-[4-(NAPHTHALEN-1-YL)PHENOXY]PROPANOIC+ACID'>65W</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=65W:2-METHYL-2-[4-(NAPHTHALEN-1-YL)PHENOXY]PROPANOIC+ACID'>65W</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=5hyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hyk OCA], [http://pdbe.org/5hyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hyk RCSB], [http://www.ebi.ac.uk/pdbsum/5hyk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hyk ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPARA, NR1C1, PPAR ([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://proteopedia.org/fgij/fg.htm?mol=5hyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hyk OCA], [http://pdbe.org/5hyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hyk RCSB], [http://www.ebi.ac.uk/pdbsum/5hyk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hyk ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5hyk" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phenylethanolamine N-methyltransferase 3D structures|Phenylethanolamine N-methyltransferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Capelli, D]]
 [[Category: Laghezza, A]]

5hyk

From Proteopedia

Revision as of 08:36, 27 May 2020

Crystal structure of the complex PPARalpha/AL26-29

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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