View source for 2v8x


==Crystallographic and mass spectrometric characterisation of eIF4E with N7-cap derivatives==
<StructureSection load='2v8x' size='340' side='right'caption='[[2v8x]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v8x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V8X FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGQ:7-BENZYL+GUANINE+MONOPHOSPHATE'>MGQ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2v8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v8x OCA], [https://pdbe.org/2v8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v8x RCSB], [https://www.ebi.ac.uk/pdbsum/2v8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v8x ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IF4E_HUMAN 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.<ref>PMID:16271312</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v8/2v8x_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v8x ConSurf].
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== Publication Abstract from PubMed ==
Structural complexes of the eukaryotic translation initiation factor 4E (eIF4E) with a series of N(7)-alkylated guanosine derivative mRNA cap analogue structures have been characterised. Mass spectrometry was used to determine apparent gas-phase equilibrium dissociation constants (K(d)) values of 0.15 microM, 13.6 microM, and 55.7 microM for eIF4E with 7-methyl-GTP (m(7)GTP), GTP, and GMP, respectively. For tight and specific binding to the eIF4E mononucleotide binding site, there seems to be a clear requirement for guanosine derivatives to possess both the delocalised positive charge of the N(7)-methylated guanine system and at least one phosphate group. We show that the N(7)-benzylated monophosphates 7-benzyl-GMP (Bn(7)GMP) and 7-(p-fluorobenzyl)-GMP (FBn(7)GMP) bind eIF4E substantially more tightly than non-N(7)-alkylated guanosine derivatives (K(d) values of 7.0 microM and 2.0 microM, respectively). The eIF4E complex crystal structures with Bn(7)GMP and FBn(7)GMP show that additional favourable contacts of the benzyl groups with eIF4E contribute binding energy that compensates for loss of the beta and gamma-phosphates. The N(7)-benzyl groups pack into a hydrophobic pocket behind the two tryptophan side-chains that are involved in the cation-pi stacking interaction between the cap and the eIF4E mononucleotide binding site. This pocket is formed by an induced fit in which one of the tryptophan residues involved in cap binding flips through 180 degrees relative to structures with N(7)-methylated cap derivatives. This and other observations made here will be useful in the design of new families of eIF4E inhibitors, which may have potential therapeutic applications in cancer.

Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives.,Brown CJ, McNae I, Fischer PM, Walkinshaw MD J Mol Biol. 2007 Sep 7;372(1):7-15. Epub 2007 Jun 15. PMID:17631896<ref>PMID:17631896</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brown CJ]]
[[Category: Fischer PM]]
[[Category: Mcnae I]]
[[Category: Walkinshaw MD]]