Pubblicazione scientifica

Rational Modification of Estrogen Receptor by Combination of Computational and Experimental Analysis

FILONE TECNOLOGICO	TEMA
produzione e raccolta	composizione alimenti/nutrienti per l’allevamento metodi di allevamento: specie ittiche da allevamento metodi di riproduzione (micro alghe, molluschi, ecc.)

RIASSUNTO

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.

DATA

Data di pubblicazione: 30/07/2014

AUTORI

FERRERO VALENTINA ELISABETTA VIVIANA
PEDOTTI MATTIA
CHIADO ALESSANDRO
SIMONELLI LUCA
CALZOLAI LUIGI
VARANI LUCA
LETTIERI TERESA

ENTE DI AFFERENZA

EUR COMMISSION DIRECTORATE GEN JOINT RSCH CTR INST ENVIRONMENT & SUSTAINABILITY ISPRA VARESE ITALY
INST RSCH IN BIOMEDICINE BELLINZONA SWITZERLAND
EUR COMMISSION DIRECTORATE GEN JOINT RSCH CTR INST HEALTH & CONSUMER PROTECTION ISPRA VARESE ITALY
BIOINFORMATICS INST SINGAPORE

RIVISTA

PLoS ONE, 9(7), e102658

IMPACT FACTOR

2,870

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