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2znn

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Revision as of 07:37, 18 October 2018

Human PPAR alpha ligand binding domain in complex with a synthetic agonist TIPP703

Structural highlights

2znn 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:
Related:	2zno, 2znp, 2znq
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]

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

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARalpha and PPARgamma LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD-ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARdelta LBD in complex with an alpha/delta-selective ligand, TIPP-401, and with a related delta-specific ligand, TIPP-204, were also determined. The comparison between the two PPARdelta complexes revealed how each ligand exhibits either a ;dual selective' or ;single specific' binding mode.

Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures.,Oyama T, Toyota K, Waku T, Hirakawa Y, Nagasawa N, Kasuga JI, Hashimoto Y, Miyachi H, Morikawa K Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):786-95. Epub 2009, Jul 10. PMID:19622862^[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
↑ Oyama T, Toyota K, Waku T, Hirakawa Y, Nagasawa N, Kasuga JI, Hashimoto Y, Miyachi H, Morikawa K. Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):786-95. Epub 2009, Jul 10. PMID:19622862 doi:10.1107/S0907444909015935

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/2znn"

@@ Line 7: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zno|2zno]], [[2znp|2znp]], [[2znq|2znq]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2znn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2znn OCA], [http://pdbe.org/2znn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2znn RCSB], [http://www.ebi.ac.uk/pdbsum/2znn PDBsum]</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=2znn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2znn OCA], [http://pdbe.org/2znn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2znn RCSB], [http://www.ebi.ac.uk/pdbsum/2znn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2znn ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zn/2znn_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zn/2znn_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2znn

From Proteopedia

Revision as of 07:37, 18 October 2018

Human PPAR alpha ligand binding domain in complex with a synthetic agonist TIPP703

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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