4DUM: Co-Crystal Structure Of Eif4e With Inhibitor

Citation:
Abstract
The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5' terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay. More importantly, the compound has an IC(50) of 2.5 muM for inhibiting cap-dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT). This series of potent, truncated analogues could serve as a promising new starting point toward the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.
PDB ID: 4DUMDownload
MMDB ID: 98744
PDB Deposition Date: 2012/2/22
Updated in MMDB: 2012/06
Experimental Method:
x-ray diffraction
Resolution: 2.95  Å
Source Organism:
Similar Structures:
Biological Unit for 4DUM: monomeric; determined by author and by software (PISA)
Molecular Components in 4DUM
Label Count Molecule
Protein (1 molecule)
1
Eukaryotic Translation Initiation Factor 4E(Gene symbol: EIF4E)
Molecule annotation
Chemicals (3 molecules)
1
1
2
2
* Click molecule labels to explore molecular sequence information.

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