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Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

View Article: PubMed Central - PubMed

ABSTRACT

Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors.

No MeSH data available.


Chemical structure of ER ligands.
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ijerph-13-00869-f001: Chemical structure of ER ligands.

Mentions: The HDX profile was analyzed for eight phytoestrogens and mycoestrogens. The binding data was presented from previously published literatures. Total of 45 informative peptides were successfully analyzed in the HDX analysis rendering 90% sequence coverage of the whole ERαLBD. Based on pervious observations [27,30], the exchange times chosen for the current experiments are 0 min, 15 min and 60 min. The hydrogen deuterium exchange value used for the statistical analysis was the average of triplicate experiment results. The chemical structures of the eight environmental estrogens together with estradiol and two SERM molecules are shown in Figure 1.


Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α
Chemical structure of ER ligands.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036702&req=5

ijerph-13-00869-f001: Chemical structure of ER ligands.
Mentions: The HDX profile was analyzed for eight phytoestrogens and mycoestrogens. The binding data was presented from previously published literatures. Total of 45 informative peptides were successfully analyzed in the HDX analysis rendering 90% sequence coverage of the whole ERαLBD. Based on pervious observations [27,30], the exchange times chosen for the current experiments are 0 min, 15 min and 60 min. The hydrogen deuterium exchange value used for the statistical analysis was the average of triplicate experiment results. The chemical structures of the eight environmental estrogens together with estradiol and two SERM molecules are shown in Figure 1.

View Article: PubMed Central - PubMed

ABSTRACT

Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors.

No MeSH data available.