Water-Bridge Mediates Recognition of mRNA Cap in eIF4E.

Dilraj Lama, Mohan R Pradhan, Christopher J Brown, Rohan S Eapen, Thomas L Joseph, Chee-Keong Kwoh, David P Lane, Chandra S Verma

Structure (London, England : 1993) 2017 Jan 03

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Ligand binding pockets in proteins contain water molecules, which play important roles in modulating protein-ligand interactions. Available crystallographic data for the 5' mRNA cap-binding pocket of the translation initiation factor protein eIF4E shows several structurally conserved waters, which also persist in molecular dynamics simulations. These waters engage an intricate hydrogen-bond network between the cap and protein. Two crystallographic waters in the cleft of the pocket show a high degree of conservation and bridge two residues, which are part of an evolutionarily conserved scaffold. This appears to be a preformed recognition module for the cap with the two structural waters facilitating an efficient interaction. This is also recapitulated in a new crystal structure of the apo protein. These findings open new windows for the design and screening of compounds targeting eIF4E. Copyright © 2016 Elsevier Ltd. All rights reserved.

Citation

Dilraj Lama, Mohan R Pradhan, Christopher J Brown, Rohan S Eapen, Thomas L Joseph, Chee-Keong Kwoh, David P Lane, Chandra S Verma. Water-Bridge Mediates Recognition of mRNA Cap in eIF4E. Structure (London, England : 1993). 2017 Jan 03;25(1):188-194