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 ER-ligand complexes with computational analysis, we were able to predict ER 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 IC50 value of 2 nM for the 17α−Ethinylestradiol ligand. Due to increased affinity and stability, utilizing such mutated ERs instead of the wild type ER as bio-recognition element would be beneficial in an assay or biosensor.
FERRERO Valentina;
PEDOTTI Mattia;
CHIADO' Alessandro;
SIMONELLI L.;
CALZOLAI Luigi;
VARANI Luca;
LETTIERI Teresa;
2014-09-02
PUBLIC LIBRARY SCIENCE
JRC89207
1932-6203,
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0102658,
https://publications.jrc.ec.europa.eu/repository/handle/JRC89207,
10.1371/journal.pone.0102658,
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