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The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex.

ABSTRACT: 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.

SUBMITTER: Salvi N

PROVIDER: S-EPMC5022372 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex.

Salvi Nicola N Papadopoulos Evangelos E Blackledge Martin M Wagner Gerhard G

Angewandte Chemie (International ed. in English) 20160510 25

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 fl ...[more]

PMID: 27162083

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