4dum

From Proteopedia

(Difference between revisions)

Revision as of 15:02, 5 August 2016

Co-crystal structure of eIF4E with inhibitor

Structural highlights

4dum is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4dt6
Gene:	EIF4E, EIF4EL1, EIF4F (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

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 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 IC50 of 2.5 M 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 towards the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.

Structure-guided design, synthesis and evaluation of guanine-derived inhibitors of the eIF4E mRNA-cap interaction.,Chen X, Kopecky D, Mihalic J, Jeffries S, Min X, Heath J, Deignan J, Sujen L, Fu Z, Guimaraes C, Li S, Johnstone S, Xu H, Cardozo M, Shen W, Walker N, Kayser F, Wang Z J Med Chem. 2012 Mar 29. PMID:22458568^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, Miyagawa H, Kitamura K, Miura K, Ishida T. Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. Biochim Biophys Acta. 2005 Dec 1;1753(2):191-208. Epub 2005 Aug 24. PMID:16271312 doi:10.1016/j.bbapap.2005.07.023
↑ Chen X, Kopecky D, Mihalic J, Jeffries S, Min X, Heath J, Deignan J, Sujen L, Fu Z, Guimaraes C, Li S, Johnstone S, Xu H, Cardozo M, Shen W, Walker N, Kayser F, Wang Z. Structure-guided design, synthesis and evaluation of guanine-derived inhibitors of the eIF4E mRNA-cap interaction. J Med Chem. 2012 Mar 29. PMID:22458568 doi:10.1021/jm300037x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dum"

@@ Line 1: / Line 1: @@
 ==Co-crystal structure of eIF4E with inhibitor==
 <StructureSection load='4dum' size='340' side='right' caption='[[4dum]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dum]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DUM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dum]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DUM FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HLI:(4-{7-[2-(4-CHLOROPHENOXY)ETHYL]-2-(METHYLAMINO)-6-OXO-6,7-DIHYDRO-1H-PURIN-8-YL}PHENYL)PHOSPHONIC+ACID'>HLI</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dt6|4dt6]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E, EIF4EL1, EIF4F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E, EIF4EL1, EIF4F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dum OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dum RCSB], [http://www.ebi.ac.uk/pdbsum/4dum PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dum OCA], [http://pdbe.org/4dum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dum RCSB], [http://www.ebi.ac.uk/pdbsum/4dum PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dum ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dum" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Johnstone, S]]
 [[Category: Min, X]]

4dum

From Proteopedia

Revision as of 15:02, 5 August 2016

Co-crystal structure of eIF4E with inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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