Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism

2002 ◽  
Author(s):  
Andrew K. Shiau ◽  
Danielle Barstad ◽  
James T. Radek ◽  
Marvin J. Meyers ◽  
Kendall W. Nettles ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Structural Characterization ◽  
Receptor Antagonism ◽  
Selective Ligand ◽  
Subtype Selective

Characterization of Soybean Germinated Embryo Extract as an Estrogen Receptor Subtype-Selective and Tissue-Specific Modulator

2019 ◽  
Vol 22 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Hyesoo Jeong ◽  
Jimin Lee ◽  
Soolin Kim ◽  
Sujeong Park ◽  
Hwasun Yang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Receptor Subtype ◽  
Tissue Specific ◽  
Embryo Extract ◽  
Subtype Selective

scholarly journals Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-β-Selective Ligand, Diarylpropionitrile

2003 ◽  
Vol 17 (2) ◽  
pp. 247-258 ◽  
Author(s):  
Jun Sun ◽  
Jerome Baudry ◽  
John A. Katzenellenbogen ◽  
Benita S. Katzenellenbogen
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Molecular Basis ◽  
Binding Pocket ◽  
Ligand Binding Pocket ◽  
Selective Ligand ◽  
Selective Ligands ◽  
Human Estrogen Receptor ◽  
Subtype Selective ◽  
Selective Character

Abstract Although the two subtypes of the human estrogen receptor (ER), ERα and ERβ, share only 56% amino acid sequence identity in their ligand binding domain (LBD), the residues that surround the ligand are nearly identical; nevertheless, subtype-selective ligands are known. To understand the molecular basis by which diarylpropionitrile (DPN), an ERβ-selective ligand, is able to discriminate between the two ERs, we examined its activity on ER mutants and chimeric constructs generated by DNA shuffling. The N-terminal region of the ERβ LBD (through helix 6) appears to be fully responsible for the ERβ selectivity of DPN. In fact, a single ERα point mutation (L384M) was largely sufficient to switch the DPN response of this ER to that of the ERβ type, but residues in helix 3 are also important in achieving the full ERβ selectivity of DPN. Using molecular modeling, we found an energetically favorable fit for the S-DPN enantiomer in ERβ, in which the proximal phenol mimics the A ring of estradiol, and the nitrile engages in stabilizing interactions with residues in the ligand-binding pocket of ERβ. Our findings highlight that a limited number of critical interactions of DPN with the ERβ ligand-binding pocket underlie its ER subtype-selective character.

Structural characterization of the trypsinized estrogen receptor

Biochemistry ◽  
1993 ◽  
Vol 32 (50) ◽  
pp. 14000-14008 ◽  
Author(s):  
Michael Fritsch ◽  
Iain Anderson ◽  
Jack Gorski
Keyword(s):  
Estrogen Receptor ◽  
Structural Characterization
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