Water-Bridge Mediates Recognition of mRNA Cap in eIF4E Lama, Dilraj et al. Structure , Volume 25 , Issue 1 , 188 - 194
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.
Computational resource for the project was supported by an A*PRE*COT (PRE-COT 2010-14) grant, Singapore. M.R.P. was funded by the Research Scholarship Award by Bioinformatics Institute-NTU/SCE Joint PhD Program. D.L. was partly funded by Ipsen Pharmaceuticals.
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