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The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex
Author(s) -
Salvi Nicola,
Papadopoulos Evangelos,
Blackledge Martin,
Wagner Gerhard
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201603254
Subject(s) - eif4g , eif4e , translation (biology) , dynamics (music) , chemistry , psychology , biochemistry , messenger rna , gene , pedagogy
Lack of regulation of the interaction between the eIF4E/eIF4G subunits of the translation initiation factor complex eIF4F is a hallmark of cancer. The inhibitor 4EGI‐1 binds to eIF4E, thereby preventing association with eIF4G through an allosteric mechanism. NMR spectroscopy and MD simulations were used to obtain a mechanistic description of the role of correlated dynamics in this allosteric regulation. We show that binding of 4EGI‐1 perturbs native correlated motions and increases correlated fluctuations in part of the eIF4G binding site.