3D model of amphioxus steroid receptor complexed with estradiol

Baker, Michael E.; Chang, David J.

doi:10.1016/j.bbrc.2009.06.079

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…Interestingly, BfER and BbER repress activation of BfSR and BbSR, respectively, by E2, suggesting a novel cross-regulatory interaction between these two receptors. The affinity of E2 for BfSR is about 100 nM [36], which makes it unlikely that E2 is the physiological ligand [41]. Other steroids may be the physiological ligands [6, 35,42] Invertebrate ERs in mollusks.…”

Section: Amphioxus Contains Steroid Receptorsmentioning

confidence: 99%

Origin and diversification of steroids: Co-evolution of enzymes and nuclear receptors

Baker

2011

Molecular and Cellular Endocrinology

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Section: Amphioxus Contains Steroid Receptorsmentioning

confidence: 99%

Origin and diversification of steroids: Co-evolution of enzymes and nuclear receptors

Baker

2011

Molecular and Cellular Endocrinology

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“…The distances between MBP and ERα are shown in Figure 2A and Table 1. For comparison, in Figure 3A and Table 2 we show the distances between E2 and human ERα [33], [35], [36], [37], [38].…”

Section: Resultsmentioning

confidence: 99%

“…Interaction of E2 with human ERα [24], [33], [34], [36], [37], [38], [39]. The phenolic hydroxyl of E2 contacts Glu-353, Arg-394 and Leu-387.…”

Section: Methodsmentioning

confidence: 99%

3D Models of MBP, a Biologically Active Metabolite of Bisphenol A, in Human Estrogen Receptor α and Estrogen Receptor β

Baker

Chandsawangbhuwana

2012

PLoS ONE

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Bisphenol A [BPA] is a widely dispersed environmental chemical that is of much concern because the BPA monomer is a weak transcriptional activator of human estrogen receptor α [ERα] and ERβ in cell culture. A BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene [MBP], has transcriptional activity at nM concentrations, which is 1000-fold lower than the concentration for estrogenic activity of BPA, suggesting that MBP may be an environmental estrogen. To investigate the structural basis for the activity of MBP at nM concentrations and the lower activity of BPA for human ERα and ERβ, we constructed 3D models of human ERα and ERβ with MBP and BPA for comparison with estradiol in these ERs. These 3D models suggest that MBP, but not BPA, has key contacts with amino acids in human ERα and ERβ that are important in binding of estradiol by these receptors. Metabolism of BPA to MBP increases the spacing between two phenolic rings, resulting in contacts between MBP and ERα and ERβ that mimic those of estradiol with these ERs. Mutagenesis of residues on these ERs that contact the phenolic hydroxyls will provide a test for our 3D models. Other environmental chemicals containing two appropriately spaced phenolic rings and an aliphatic spacer instead of an estrogenic B and C ring also may bind to ERα or ERβ and interfere with normal estrogen physiology. This analysis also may be useful in designing novel chemicals for regulating the actions of human ERα and ERβ.

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“…Nuclear receptors with transcriptional responses to adrenal and sex steroids appear to have evolved in deuterostomes [5][6][7]; the estrogen receptor [ER] is the ancestral vertebrate steroid receptor [6][7][8][9][10][11]. [8][9][12][13][14]. Although mollusks and annelids contain receptors with sequence similarity to the human ER [15][16][17], there is disagreement as to whether these protostome receptors diverged from a common ancestor of chordate ER [17], or if the similarity between protostome proteins and the chordate ER is an example of convergent evolution [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

3D model of amphioxus steroid receptor complexed with estradiol

Cited by 12 publications

References 35 publications

Origin and diversification of steroids: Co-evolution of enzymes and nuclear receptors

Origin and diversification of steroids: Co-evolution of enzymes and nuclear receptors

3D Models of MBP, a Biologically Active Metabolite of Bisphenol A, in Human Estrogen Receptor α and Estrogen Receptor β

Insights from the structure of estrogen receptor into the evolution of estrogens: Implications for endocrine disruption

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