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European Biophysics Journal

, Volume 39, Issue 11, pp 1471–1475 | Cite as

A canonical cation–π interaction stabilizes the agonist conformation of estrogen-like nuclear receptors

  • Núria Queralt-Rosinach
  • Jordi MestresEmail author
Original Paper

Abstract

Representative crystal structures of the ligand-binding domain for the majority of nuclear receptors are currently available. A systematic comparative analysis of these structures identified an energetically favorable cation–π interaction that involves an amino acid located at the extreme C-terminal end and appears to form only in the agonist conformation of the estrogen receptor α, glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. It is postulated that this cation–π interaction is used by members of the estrogen-like subfamily to provide additional stabilization to the transcriptional active conformation upon ligand binding.

Keywords

Protein stability Side-directed mutagenesis Drug design Agonist binding 

Notes

Acknowledgments

Grant sponsor: Spanish Ministerio de Educación y Ciencia and Instituto de Salud Carlos III; Grant number: BIO2008-02329.

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Copyright information

© European Biophysical Societies' Association 2010

Authors and Affiliations

  1. 1.Chemogenomics Laboratory, Research Program on Biomedical Informatics (GRIB)Institut Municipal d’Investigació Mèdica and Universitat Pompeu FabraBarcelonaSpain

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