Journal article

Rational modification of estrogen receptor by combination of computational and experimental analysis

  • Ferrero, Valentina Elisabetta Viviana European Commission - Directorate General - Joint Research Centre, Institute for Environment and Sustainability, Ispra, Varese, Italy
  • Pedotti, Mattia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Chiadò, Alessandro Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Simonelli, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Calzolai, Luigi European Commission - Directorate General - Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Varese, Italy
  • Varani, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Lettieri, Teresa European Commission - Directorate General - Joint Research Centre, Institute for Environment and Sustainability, Ispra, Varese, Italy
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    30.07.2014
Published in:
  • Plos one. - 2014, vol. 9, no. 7, p. e102658
English In this manuscript, we modulate the binding properties of estrogen receptor protein by rationally modifying the amino acid composition of its ligand binding domain. By combining sequence alignment and structural analysis of known estrogen receptor- ligand complexes with computational analysis, we were able to predict estrogen receptor mutants with altered binding properties. These predictions were experimentally confirmed by producing single point variants with up to an order of magnitude increased binding affinity towards some estrogen disrupting chemicals and reaching an half maximal inhibitory concentration (IC50) value of 2 nM for the 17α- ethinylestradiol ligand. Due to increased affinity and stability, utilizing such mutated estrogen receptor instead of the wild type as bio-recognition element would be beneficial in an assay or biosensor.
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  • English
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Chemistry
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https://susi.usi.ch/usi/documents/319013
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