6kxy

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:46, 22 November 2023) (edit) (undo)
 
Line 1: Line 1:
==Human PPAR alpha ligand binding domain in complex with a synthetic agonist (compound B)==
==Human PPAR alpha ligand binding domain in complex with a synthetic agonist (compound B)==
-
<StructureSection load='6kxy' size='340' side='right'caption='[[6kxy]]' scene=''>
+
<StructureSection load='6kxy' size='340' side='right'caption='[[6kxy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KXY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KXY FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6kxy]] 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=6KXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KXY FirstGlance]. <br>
-
</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=6kxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kxy OCA], [http://pdbe.org/6kxy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kxy RCSB], [http://www.ebi.ac.uk/pdbsum/6kxy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kxy ProSAT]</span></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&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T06:6-ethyl-1-(4-fluorophenyl)-3-pentan-3-yl-pyrazolo[3,4-b]pyridine-4-carboxylic+acid'>T06</scene></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=6kxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kxy OCA], [https://pdbe.org/6kxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kxy RCSB], [https://www.ebi.ac.uk/pdbsum/6kxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kxy ProSAT]</span></td></tr>
</table>
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/PPARA_HUMAN 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.<ref>PMID:7684926</ref> <ref>PMID:7629123</ref> <ref>PMID:9556573</ref> <ref>PMID:10195690</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Small-molecule agonism of peroxisome proliferator-activated receptor alpha (PPARalpha), a ligand-activated transcriptional factor involved in regulating fatty acid metabolism, is an important approach for treating dyslipidemia. Here, we determined the structures of the ligand-binding domain (LBD) of PPARalpha in complex with 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivatives, which were recently identified as PPARalpha-selective activators with markedly different structures from those of the well-known PPARalpha agonists fibrates. The crystal structures of the complexes showed that they form a canonical hydrogen-bond network involving helix 12 in the LBD, which is thought to be essential for PPARalpha activation, as also observed for fibrates. However, the phenyl side chain of the compounds occupies a small cavity between Ile272 and Ile354, which is rarely accessed by fibrates. This unique feature may be essential for subtype selectivity and combine with the well-characterized binding mode of fibrates to improve activity. These findings demonstrate the advantage of using 1H-pyrazolo-[3,4-b]pyridine as a skeleton of PPARalpha agonists and provide insight into the design of molecules for treating dyslipidemia.
 +
 +
Structural Basis for PPARalpha Activation by 1H-pyrazolo-[3,4-b]pyridine Derivatives.,Yoshida T, Oki H, Doi M, Fukuda S, Yuzuriha T, Tabata R, Ishimoto K, Kawahara K, Ohkubo T, Miyachi H, Doi T, Tachibana K Sci Rep. 2020 May 6;10(1):7623. doi: 10.1038/s41598-020-64527-x. PMID:32376995<ref>PMID:32376995</ref>
 +
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 6kxy" style="background-color:#fffaf0;"></div>
 +
 +
==See Also==
 +
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
 +
== References ==
 +
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Doi M]]
[[Category: Doi M]]

Current revision

Human PPAR alpha ligand binding domain in complex with a synthetic agonist (compound B)

PDB ID 6kxy

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6kxy"
Personal tools