Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors.
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Suetsugi M, Su L, Karlsberg K, Yuan YC, Chen S
Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors.
Mol Cancer Res. 2003 Nov;1(13):981-91.
- PubMed ID
- 14638870 [ View in PubMed]
- Abstract
While estrogen-related receptors (ERRalpha, ERRbeta, and ERRgamma) share a high amino acid sequence homology with estrogen receptors (ERs), estrogens are not ligands of ERRs. Structure-function studies from this and other laboratories have revealed that ERRs have small ligand-binding pockets and have provided evidence to show that these receptors can activate gene transcription in a constitutive manner. To address the question as to whether there is any agonist for ERRs, our laboratory recently performed virtual ligand screening on ERRalpha that predicted flavone and isoflavone phytoestrogens to be ligands of this receptor. Our mammalian cell transfection and mammalian two-hybrid experiments revealed that three isoflavones (genistein, daidzein, and biochanin A) and one flavone (6,3',4'-trihydroxyflavone) behaved as agonists of ERRs. These phytoestrogens induced the activity of ERRalpha at concentrations that are comparable to those for the activation of ERalpha and ERbeta. In this study, we also used the results of ERRalpha ligand-binding site mutant, F232A, to verify our ERRalpha hypothetical computer model. Our recent ERR research has determined for the first time that flavone and isoflavone phytoestrogens are agonists of ERRs. In addition, our studies have demonstrated that an approach that combines structure-based virtual screening and receptor functional assays can identify novel ligands of orphan nuclear receptors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Flavone Steroid hormone receptor ERR1 Protein Humans UnknownAgonistDetails Flavone Steroid hormone receptor ERR2 Protein Humans UnknownAgonistDetails Genistein Steroid hormone receptor ERR1 Protein Humans UnknownAgonistDetails Genistein Steroid hormone receptor ERR2 Protein Humans UnknownAgonistDetails