Water-Bridge Mediates Recognition of mRNA Cap in eIF4E
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 a...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/84992 http://hdl.handle.net/10220/42071 |
| Summary: | 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. |
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