8sx4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of eIF4e in complex with Compound 7n== | |
| + | <StructureSection load='8sx4' size='340' side='right'caption='[[8sx4]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8sx4]] is a 2 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=8SX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SX4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</scene>, <scene name='pdbligand=WXL:[(~{Z})-4-[2-azanyl-7-[(5-chloranyl-1~{H}-indol-2-yl)methyl]-6-oxidanylidene-1~{H}-purin-9-yl]but-2-enyl]phosphonic+acid'>WXL</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=8sx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sx4 OCA], [https://pdbe.org/8sx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sx4 RCSB], [https://www.ebi.ac.uk/pdbsum/8sx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sx4 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Eukaryotic translation initiation factor 4E (eIF4E) is an RNA-binding protein that binds to the m (7) GpppX-cap at the 5' terminus of coding mRNAs to initiate cap-dependent translation. While all cells require cap-dependent translation, cancer cells become addicted to enhanced translational capacity, driving the production of oncogenic proteins involved in proliferation, evasion of apoptosis, metastasis, and angiogenesis among other cancerous phenotypes. eIF4E is the rate-limiting translation factor and its activation has been shown to drive cancer initiation, progression, metastasis, and drug resistance. These findings have established eIF4E as a translational oncogene and promising, albeit challenging, anti-cancer therapeutic target. Although significant effort has been put forth towards inhibiting eIF4E, the design of cell-permeable, cap-competitive inhibitors remains a challenge. Herein, we describe our work towards solving this long-standing challenge. By employing an acyclic nucleoside phosphonate prodrug strategy, we report the synthesis of cell-permeable inhibitors of eIF4E binding to capped mRNA to inhibit cap-dependent translation. | ||
| - | + | Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.,Cardenas EL, O'Rourke RL, Menon A, Meagher J, Stuckey J, Garner AL bioRxiv. 2023 May 24:2023.05.23.541912. doi: 10.1101/2023.05.23.541912. Preprint. PMID:37292917<ref>PMID:37292917</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8sx4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Meagher JL]] | ||
| + | [[Category: Stuckey JA]] | ||
Revision as of 09:43, 21 June 2023
Crystal Structure of eIF4e in complex with Compound 7n
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