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

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 wer...

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Main Authors:	Valentina Elisabetta Viviana Ferrero, Mattia Pedotti, Alessandro Chiadò, Luca Simonelli, Luigi Calzolai, Luca Varani, Teresa Lettieri
Format:	article
Language:	EN
Published:	Public Library of Science (PLoS) 2014
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/64b1833085ed4db2a395c5ebcacef1c0
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spelling	oai:doaj.org-article:64b1833085ed4db2a395c5ebcacef1c02021-11-25T06:06:42ZRational modification of estrogen receptor by combination of computational and experimental analysis.1932-620310.1371/journal.pone.0102658https://doaj.org/article/64b1833085ed4db2a395c5ebcacef1c02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25075862/?tool=EBIhttps://doaj.org/toc/1932-6203In 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.Valentina Elisabetta Viviana FerreroMattia PedottiAlessandro ChiadòLuca SimonelliLuigi CalzolaiLuca VaraniTeresa LettieriPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102658 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valentina Elisabetta Viviana Ferrero Mattia Pedotti Alessandro Chiadò Luca Simonelli Luigi Calzolai Luca Varani Teresa Lettieri Rational modification of estrogen receptor by combination of computational and experimental analysis.
description	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.
format	article
author	Valentina Elisabetta Viviana Ferrero Mattia Pedotti Alessandro Chiadò Luca Simonelli Luigi Calzolai Luca Varani Teresa Lettieri
author_facet	Valentina Elisabetta Viviana Ferrero Mattia Pedotti Alessandro Chiadò Luca Simonelli Luigi Calzolai Luca Varani Teresa Lettieri
author_sort	Valentina Elisabetta Viviana Ferrero
title	Rational modification of estrogen receptor by combination of computational and experimental analysis.
title_short	Rational modification of estrogen receptor by combination of computational and experimental analysis.
title_full	Rational modification of estrogen receptor by combination of computational and experimental analysis.
title_fullStr	Rational modification of estrogen receptor by combination of computational and experimental analysis.
title_full_unstemmed	Rational modification of estrogen receptor by combination of computational and experimental analysis.
title_sort	rational modification of estrogen receptor by combination of computational and experimental analysis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/64b1833085ed4db2a395c5ebcacef1c0
work_keys_str_mv	AT valentinaelisabettavivianaferrero rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis AT mattiapedotti rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis AT alessandrochiado rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis AT lucasimonelli rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis AT luigicalzolai rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis AT lucavarani rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis AT teresalettieri rationalmodificationofestrogenreceptorbycombinationofcomputationalandexperimentalanalysis
_version_	1718414166498213888

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

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