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

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.

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Acknowledgments

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

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Correspondence to Jordi Mestres.

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Queralt-Rosinach, N., Mestres, J. A canonical cation–π interaction stabilizes the agonist conformation of estrogen-like nuclear receptors. Eur Biophys J 39, 1471–1475 (2010). https://doi.org/10.1007/s00249-010-0602-2

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  • DOI: https://doi.org/10.1007/s00249-010-0602-2

Keywords

  • Protein stability
  • Side-directed mutagenesis
  • Drug design
  • Agonist binding