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|Title:||Water-Bridge Mediates Recognition of mRNA Cap in eIF4E||Authors:||Lama, Dilraj
Pradhan, Mohan R.
Brown, Christopher J.
Eapen, Rohan S.
Joseph, Thomas L.
Lane, David P.
Verma, Chandra Shekhar
|Keywords:||Translation initiation factor 4E protein
5′ mRNA cap
|Issue Date:||2017||Source:||Lama, D., Pradhan, M. R., Brown, C. J., Eapen, R. S., Joseph, T. L., Kwoh, C. -K., et al. (2017). Water-Bridge Mediates Recognition of mRNA Cap in eIF4E. Structure, 25(1), 188-194.||Series/Report no.:||Structure||Abstract:||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.||URI:||https://hdl.handle.net/10356/84992
|ISSN:||0969-2126||DOI:||http://dx.doi.org/10.1016/j.str.2016.11.006||Rights:||© 2016 Elsevier Ltd. This is the author created version of a work that has been peer reviewed and accepted for publication by Structure, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.str.2016.11.006].||metadata.item.grantfulltext:||open||metadata.item.fulltext:||With Fulltext|
|Appears in Collections:||SCSE Journal Articles|
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