scholarly journals Bisphenol A derivatives act as novel coactivator binding inhibitors for estrogen receptor β

2021 ◽  
Author(s):  
Masaki Iwamoto ◽  
Takahiro Masuya ◽  
Mari Hosose ◽  
Koki Tagawa ◽  
Tomoka Ishibashi ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Wild Type ◽  
Chemical Library ◽  
Ligand Interaction ◽  
Docking Simulations ◽  
Coactivator Binding Inhibitors ◽  
Direct Binding ◽  
Interaction Position ◽  
Binding Inhibitors

Bisphenol A and its derivatives are recognized endocrine disruptors based on their complex effects on estrogen receptor (ER) signaling. While the effects of bisphenol derivatives on ERα have been thoroughly evaluated, how these chemicals affect ERβ signaling is not well understood. Herein, we identified novel ERβ ligands by screening a chemical library of bisphenol derivatives. Many of the compounds identified showed intriguing dual activities as ERα agonists and ERβ antagonists. Docking simulations suggested that these compounds act as coactivator binding inhibitors (CBIs). Direct binding experiments using wild-type and mutated ERβ demonstrated the presence of a second ligand interaction position at the coactivator binding site in ERβ. Our study is the first to propose that bisphenol derivatives act as CBIs, presenting a critical view point for future ER signaling-based drug development.

scholarly journals Bisphenol A derivatives act as novel coactivator binding inhibitors for estrogen receptor β

2021 ◽  
pp. 101173
Author(s):  
Masaki Iwamoto ◽  
Takahiro Masuya ◽  
Mari Hosose ◽  
Koki Tagawa ◽  
Tomoka Ishibashi ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Estrogen Receptor Β ◽  
Coactivator Binding Inhibitors ◽  
Binding Inhibitors

scholarly journals Estrogenic activity of lignin-derivable alternatives to bisphenol A assessed via molecular docking simulations

RSC Advances ◽  
2021 ◽  
Vol 11 (36) ◽  
pp. 22149-22158
Author(s):  
Alice Amitrano ◽  
Jignesh S. Mahajan ◽  
LaShanda T. J. Korley ◽  
Thomas H. Epps
Keyword(s):  
Estrogen Receptor ◽  
Molecular Docking ◽  
Bisphenol A ◽  
Endocrine Disruptor ◽  
Estrogen Receptor Alpha ◽  
Estrogenic Activity ◽  
Docking Simulations ◽  
Receptor Alpha ◽  
Structure Activity Relationships ◽  
Structure Activity

This article explores lignin-derivable bisphenols as alternatives to bisphenol A – a suspected endocrine disruptor – by investigating their structure-activity relationships with respect to estrogen receptor alpha via molecular docking.

scholarly journals Perturbation of Estrogen Receptor α Localization with Synthetic Nona-Arginine LXXLL-Peptide Coactivator Binding Inhibitors

2009 ◽  
Vol 16 (7) ◽  
pp. 702-711 ◽  
Author(s):  
Maëlle Carraz ◽  
Wilbert Zwart ◽  
Trang Phan ◽  
Rob Michalides ◽  
Luc Brunsveld
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Coactivator Binding Inhibitors ◽  
Binding Inhibitors

scholarly journals Synthesis of Biphenyl Proteomimetics as Estrogen Receptor-α Coactivator Binding Inhibitors

2009 ◽  
Vol 11 (23) ◽  
pp. 5370-5373 ◽  
Author(s):  
Anna B. Williams ◽  
Patrick T. Weiser ◽  
Robert N. Hanson ◽  
Jillian R. Gunther ◽  
John A. Katzenellenbogen
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Coactivator Binding Inhibitors ◽  
Binding Inhibitors

Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bone Mineral Density ◽  
Estrogen Receptor ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Female Rats ◽  
Wild Type ◽  
Mineral Density ◽  
Transgenic Rats ◽  
Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

Estrogen Receptor-Independent Catechol Estrogen Binding Activity:  Protein Binding Studies in Wild-Type, Estrogen Receptor-α KO, and Aromatase KO Mice Tissues†

Biochemistry ◽  
2004 ◽  
Vol 43 (21) ◽  
pp. 6698-6708 ◽  
Author(s):  
Brian J. Philips ◽  
Pete J. Ansell ◽  
Leslie G. Newton ◽  
Nobuhiro Harada ◽  
Shin-Ichiro Honda ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Protein Binding ◽  
Estrogen Receptor Α ◽  
Binding Activity ◽  
Wild Type ◽  
Binding Studies ◽  
Catechol Estrogen ◽  
Estrogen Binding

scholarly journals Molecular Dynamics Scoring of Protein–Peptide Models Derived from Coarse-Grained Docking

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3293
Author(s):  
Mateusz Zalewski ◽  
Sebastian Kmiecik ◽  
Michał Koliński
Keyword(s):  
Molecular Dynamics ◽  
Geometry Optimization ◽  
Computational Prediction ◽  
Md Simulations ◽  
Coarse Grained ◽  
Ligand Interaction ◽  
Vast Number ◽  
Docking Simulations ◽  
Peptide Models ◽  
Peptide Complexes

One of the major challenges in the computational prediction of protein–peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein–peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor–ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein–peptide complexes show that the proposed MD-based scoring approach can be used to identify protein–peptide models of high accuracy. The results also indicate that the scoring accuracy may be significantly affected by the quality of the reconstructed protein receptor structures.

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