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4bea

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Revision as of 10:50, 4 August 2016

Crystal Structure of eIF4E in Complex with a Stapled Peptide Derivative

Structural highlights

4bea is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
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

eIF4E is frequently over-expressed in different cancers and causes increased translation of oncogenic proteins via deregulated cap-dependent translation. Inhibitors of the eIF4E:eIF4G interactions represent an approach that would normalize cap-dependent translation. Stapled peptides represent an emerging class of therapeutics that can target protein: protein interactions. We present here molecular dynamics simulations for a set of rationally designed stapled peptides in solution and in complex with eIF4E, supported with biophysical and crystallographic data. Clustering of the simulated structures revealed the favoured conformational states of the stapled peptides in their bound or free forms in solution. Identifying these populations has allowed us to design peptides with improved affinities by introducing mutations into the peptide sequence to alter their conformational distributions. These studies emphasise the effects that engineered mutations have on the conformations of free and bound peptides, and illustrate that both states must be considered in efforts to attain high affinity binding.

Rational Optimization of Conformational Effects Induced By Hydrocarbon Staples in Peptides and their Binding Interfaces.,Lama D, Quah ST, Verma CS, Lakshminarayanan R, Beuerman RW, Lane DP, Brown CJ Sci Rep. 2013 Dec 13;3:3451. doi: 10.1038/srep03451. PMID:24336354^[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
↑ Lama D, Quah ST, Verma CS, Lakshminarayanan R, Beuerman RW, Lane DP, Brown CJ. Rational Optimization of Conformational Effects Induced By Hydrocarbon Staples in Peptides and their Binding Interfaces. Sci Rep. 2013 Dec 13;3:3451. doi: 10.1038/srep03451. PMID:24336354 doi:http://dx.doi.org/10.1038/srep03451

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/4bea"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of eIF4E in Complex with a Stapled Peptide Derivative==
 <StructureSection load='4bea' size='340' side='right' caption='[[4bea]], [[Resolution|resolution]] 2.57&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4bea]] is a 2 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=4BEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BEA FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NME:METHYLAMINE'>NME</scene></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=4bea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bea OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bea RCSB], [http://www.ebi.ac.uk/pdbsum/4bea 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=4bea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bea OCA], [http://pdbe.org/4bea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bea RCSB], [http://www.ebi.ac.uk/pdbsum/4bea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bea ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4bea" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Eukaryotic initiation factor|Eukaryotic initiation factor]]
 == References ==
 <references/>

4bea

From Proteopedia

Revision as of 10:50, 4 August 2016

Crystal Structure of eIF4E in Complex with a Stapled Peptide Derivative

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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