View source for 7kma


==Crystal structure of eif2Balpha with a ligand.==
<StructureSection load='7kma' size='340' side='right'caption='[[7kma]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kma]] is a 8 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=7KMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KMA 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=M6P:ALPHA-D-MANNOSE-6-PHOSPHATE'>M6P</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=7kma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kma OCA], [https://pdbe.org/7kma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kma RCSB], [https://www.ebi.ac.uk/pdbsum/7kma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kma 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 ==
The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. The eIF2B regulatory subcomplex is evolutionarily related to sugar-metabolizing enzymes, but the biological relevance of this relationship was unknown. To identify natural ligands that might regulate eIF2B, we conduct unbiased binding- and activity-based screens followed by structural studies. We find that sugar phosphates occupy the ancestral catalytic site in the eIF2Balpha subunit, promote eIF2B holoenzyme formation and enhance enzymatic activity towards eIF2. A mutant in the eIF2Balpha ligand pocket that causes Vanishing White Matter disease fails to engage and is not stimulated by sugar phosphates. These data underscore the importance of allosteric metabolite modulation for proper eIF2B function. We propose that eIF2B evolved to couple nutrient status via sugar phosphate sensing with the rate of protein synthesis, one of the most energetically costly cellular processes.

Sugar phosphate activation of the stress sensor eIF2B.,Hao Q, Heo JM, Nocek BP, Hicks KG, Stoll VS, Remarcik C, Hackett S, LeBon L, Jain R, Eaton D, Rutter J, Wong YL, Sidrauski C Nat Commun. 2021 Jun 8;12(1):3440. doi: 10.1038/s41467-021-23836-z. PMID:34103529<ref>PMID:34103529</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kma" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hao Q]]
[[Category: Nocek B]]
[[Category: Remarcik C]]
[[Category: Sidrauski C]]
[[Category: Stoll V]]
[[Category: Wong Y]]