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Updated: Jul 27, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
The estrogen receptor: a structure-based approach to the design of new specific hormone-receptor combinations
R Tedesco1, J A Thomas, B S Katzenellenbogen
1Department of Chemistry, University of Illinois, Urbana 61801, USA.
Background:
The specificity of hormone action arises from complementary steric and electronic interactions between a hormonal ligand and its cognate receptor. An analysis of such key ligand-receptor contact sites, often delineated by mutational mapping and X-ray crystallographic studies, can suggest ways in which hormone-receptor specificity might be altered.
Results:
We have altered the hormonal specificity of the estrogen receptor alpha (ER) by making 'coordinated' changes in the A-ring of the ligand estradiol and in the A-ring binding subpocket of ER. These changes were designed to maintain a favorable interaction when both E and ER are changed, but to disfavor interaction when only E or ER is changed. We have evaluated several of these altered ligand and receptor pairs in quantitative ligand binding and reporter gene assays.
Conclusions:
In best cases, the new interaction is sufficiently favorable and orthogonal so as to represent the creation of a new hormone specificity, which might be useful in the regulation of transgene activity.
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