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Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex.
Angewandte Chemie 2016 June 14
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.
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