View source for 9zuz


==Translation Initiation Factor eIF-2B complex with the Isohexide Diamine GSK735==
<StructureSection load='9zuz' size='340' side='right'caption='[[9zuz]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9zuz]] is a 3 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=9ZUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZUZ 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]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C32:~{N}-[(3~{S},3~{a}~{R},6~{R},6~{a}~{R})-6-[2-(4-chloranylphenoxy)ethanoylamino]-2,3,3~{a},5,6,6~{a}-hexahydrofuro[3,2-b]furan-3-yl]-2-(4-chloranylphenoxy)ethanamide'>A1C32</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9zuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zuz OCA], [https://pdbe.org/9zuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zuz RCSB], [https://www.ebi.ac.uk/pdbsum/9zuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zuz 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 ==
ISRIB reactivates protein synthesis for cells under stress through the stabilization of eukaryotic initiation factor 2 beta (eIF2B). We discovered that diaminoisohexides, derived from isomannide and isosorbide serve as a bioisostere for the diamino cyclohexane core in ISRIB. These scaffolds conferred improved solubility but also showed activity for the human ether-a-go-go-related gene (hERG). Herein we describe our efforts to mitigate hERG activity while maintaining target potency. The first high resolution (2.25A) X-ray cocrystal structure of the eIF2B (alpha,beta,delta)(2) complex with compound 7a is reported, which can inform subsequent SAR.

Discovery of Isohexide Bisglycolamides as Inhibitors of the Integrated Stress Response.,Colandrea VJ, Joshi-Pangu A, Nolte RT, Bledsoe RK, Ward P, Glancy J, Kowalski MD, Huff CA, Desai S, Nagilla R, Laping NJ, Axten JM, Evans KA ACS Med Chem Lett. 2026 Jan 15;17(2):495-502. doi: , 10.1021/acsmedchemlett.5c00698. eCollection 2026 Feb 12. PMID:41704357<ref>PMID:41704357</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9zuz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Nolte RT]]