9qc6: Difference between revisions

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'''Unreleased structure'''


The entry 9qc6 is ON HOLD  until Paper Publication
==Structure of eIF2B decamer bound to (P)eIF2 alpha and Compound A-(S)==
<StructureSection load='9qc6' size='340' side='right'caption='[[9qc6]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qc6]] is a 11 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=9QC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QC6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.83&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I5O:~{N}-[(1~{S})-7-[3-[[ethanoyl(methyl)amino]methyl]phenyl]-5-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]-2-[[(3~{R},4~{S})-3-fluoranylpiperidin-4-yl]methoxy]-~{N}-methyl-ethanamide'>A1I5O</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=9qc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qc6 OCA], [https://pdbe.org/9qc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qc6 RCSB], [https://www.ebi.ac.uk/pdbsum/9qc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qc6 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN] Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Eukaryotic initiation factor 2B (eIF2B), a guanine nucleotide exchange factor (GEF), promotes protein synthesis by charging translation initiation factor 2 (eIF2) with GTP. Stress-induced phosphorylation of eIF2 on its alpha-subunit [eIF2(alphaP)] inhibits this reaction triggering a protective Integrated Stress Response (ISR). A DNA-encoded chemical library (DEL) screen for modulators of eIF2B, led to the identification of a chemical series that stabilises the inactive state of eIF2B, stimulating the ISR. Cryo-EM of compound-bound eIF2B reveals a conformational switch to the inactive state engaged by eIF2(alphaP). In cells, compound activity is sensitive to eIF2's phosphorylation state and to a competing eIF2B ligand (ISRIB) that activates the GEF allosterically. These findings establish the feasibility of targeting eIF2B with a drug-like allosteric inhibitor, that serves as an ISR activator (ISRAC), paving the way to explore the therapeutic potential of eIF2B-directed ISR activation.


Authors:  
A molecular stabiliser of an inhibitory eIF2B-eIF2(alphaP) complex activates the Integrated Stress Response.,Shilliday F, Gancedo-Rodrigo M, George G, Aibara S, Adhikari S, Ashraf SN, Barrey EJ, Centrella PA, Crowther D, Dickson P, Gikunju D, Guie MA, Guilinger JP, Gunnarsson A, Harding HP, Hupp CD, Jetson R, Keefe AD, Kim JM, Lewis RJ, Maia de Oliveira T, Le-Marshall J, Narayanan U, Nugai KA, Petrovic D, Rivers E, Ron D, Stringfellow D, Syson K, Ward L, Yeoman JTS, Yu Y, Zhang Y, Zyryanova A, Baker DJ, Breccia P, Linley JE Nat Commun. 2026 May 6. doi: 10.1038/s41467-026-72688-y. PMID:42091608<ref>PMID:42091608</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9qc6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gancedo-Rodrigo M]]
[[Category: Maia de Oliveira T]]
[[Category: Shilliday F]]
Retrieved from "https://proteopedia.org/9qc6"