5gw6
From Proteopedia
Water-Bridge Mediates Recognition of mRNA Cap in eIF4E
Structural highlights
Function[IF4E_HUMAN] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.[1] Publication Abstract from PubMedLigand 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. Water-Bridge Mediates Recognition of mRNA Cap in eIF4E.,Lama D, Pradhan MR, Brown CJ, Eapen RS, Joseph TL, Kwoh CK, Lane DP, Verma CS Structure. 2017 Jan 3;25(1):188-194. doi: 10.1016/j.str.2016.11.006. Epub 2016, Dec 1. PMID:27916520[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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