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BioAssay: AID 666138

Binding affinity to N-terminal His-tagged human PPARalpha ligand binding domain assessed as increase in fluorescence at 500 nM by fluorometry

Based on X-ray crystallographic analysis of a peroxisome proliferator-activated receptor (PPAR) alpha/delta dual agonist complexed with human PPARs ligand binding domain (LBD), we previously reported the design and synthesis of a pyrene-based fluorescent PPARalpha/delta co-agonist 2. Here, we found that the fluorescence intensity of 2 increased upon binding to hPPARalpha-LBD, in a manner more ..
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Active(1)
 
 
 Tested Substances
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Active(1)
 
 
AID: 666138
Data Source: ChEMBL (823227)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-08-25

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Peroxisome proliferator-activated receptor alpha; Short=PPAR-alpha; AltName: Full=Nuclear receptor subfamily 1 group C member 1
Description ..   
Protein Family: The ligand binding domain of peroxisome proliferator-activated receptors
Comment ..   

Gene:PPARA     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Bidirectional fluorescence properties of pyrene-based peroxisome proliferator-activated receptor (PPAR) alpha/delta dual agonist.

Abstract: Based on X-ray crystallographic analysis of a peroxisome proliferator-activated receptor (PPAR) alpha/delta dual agonist complexed with human PPARs ligand binding domain (LBD), we previously reported the design and synthesis of a pyrene-based fluorescent PPARalpha/delta co-agonist 2. Here, we found that the fluorescence intensity of 2 increased upon binding to hPPARalpha-LBD, in a manner dependent upon the concentration of the LBD. But, surprisingly, the fluorescence intensity of 2 decreased concentration-dependently upon binding to hPPRdelta-LBD. Site-directed mutagenesis of the two hPPAR subtypes clearly indicated that Trp264 of hPPARdelta-LBD, located between H2' helix and H3 helix (omega loop), is critical for the concentration-dependent decrease in fluorescence intensity, which is suggested to be due to fluorescence resonance energy transfer (FRET) from the pyrene moiety of bound 2 to the nearby side-chain indole moiety of Trp264 in the hPPARdelta-LBD.
(PMID: 22551628)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

Data Table (Concise)
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