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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.


Related in: MedlinePlus

Cluster analysis of all analyzed compounds. The names of compound are shown above the bar view, and the peptide regions are shown on the right of the bar view. The color represents the differential deuterium level of each peptide in the absence and presence of compounds. The scale is presented in percentage (%).
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ijerph-13-00869-f002: Cluster analysis of all analyzed compounds. The names of compound are shown above the bar view, and the peptide regions are shown on the right of the bar view. The color represents the differential deuterium level of each peptide in the absence and presence of compounds. The scale is presented in percentage (%).

Mentions: The values in Table 2 represent the average difference in the deuterium incorporation percentages for each of the three exchange time points when comparing the apo ERαLBD to the ligand bound ERαLBD. Across the whole chemical panel, many of the phytoestrogens show various degree of protection of helix 12 from HDX exchange, indicating different binding modes compared to that of estradiol. As a whole, 45 peptides were analyzed for each ER/ligand binding complex and the multiple variate data set was used for the cluster analysis. Figure 2 reveals the cluster pattern of all the chemical compounds analyzed in this study. Interestingly, in the whole panel of eleven compounds, raloxifene, estradiol, and 4-hydroxytamoxifen were clustered together. The phytoestrogens and mycoestrogen, which include fisetin, kaempferol, resveratrol, quercetin, genistein, daidzein, coumestrol, and zearalenone, are clustered together.


Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α
Cluster analysis of all analyzed compounds. The names of compound are shown above the bar view, and the peptide regions are shown on the right of the bar view. The color represents the differential deuterium level of each peptide in the absence and presence of compounds. The scale is presented in percentage (%).
© Copyright Policy
Related In: Results  -  Collection

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

ijerph-13-00869-f002: Cluster analysis of all analyzed compounds. The names of compound are shown above the bar view, and the peptide regions are shown on the right of the bar view. The color represents the differential deuterium level of each peptide in the absence and presence of compounds. The scale is presented in percentage (%).
Mentions: The values in Table 2 represent the average difference in the deuterium incorporation percentages for each of the three exchange time points when comparing the apo ERαLBD to the ligand bound ERαLBD. Across the whole chemical panel, many of the phytoestrogens show various degree of protection of helix 12 from HDX exchange, indicating different binding modes compared to that of estradiol. As a whole, 45 peptides were analyzed for each ER/ligand binding complex and the multiple variate data set was used for the cluster analysis. Figure 2 reveals the cluster pattern of all the chemical compounds analyzed in this study. Interestingly, in the whole panel of eleven compounds, raloxifene, estradiol, and 4-hydroxytamoxifen were clustered together. The phytoestrogens and mycoestrogen, which include fisetin, kaempferol, resveratrol, quercetin, genistein, daidzein, coumestrol, and zearalenone, are clustered together.

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.


Related in: MedlinePlus