View source for 7zve


==K403 acetylated glucose-6-phosphate dehydrogenase (G6PD)==
<StructureSection load='7zve' size='340' side='right'caption='[[7zve]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zve]] 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=7ZVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZVE 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]] 2.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7zve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zve OCA], [https://pdbe.org/7zve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zve RCSB], [https://www.ebi.ac.uk/pdbsum/7zve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zve ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/G6PD_HUMAN G6PD_HUMAN] Defects in G6PD are the cause of chronic non-spherocytic hemolytic anemia (CNSHA) [MIM:[https://omim.org/entry/305900 305900]. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of CNSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.<ref>PMID:1611091</ref> 
== Function ==
[https://www.uniprot.org/uniprot/G6PD_HUMAN G6PD_HUMAN] Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is acetylated on multiple lysine residues. Using site-specifically acetylated G6PD, we show that acetylation can activate (AcK89) and inhibit (AcK403) G6PD. Acetylation-dependent inactivation is explained by structural studies showing distortion of the dimeric structure and active site of G6PD. We provide evidence for acetylation-dependent K95/97 ubiquitylation of G6PD and Y503 phosphorylation, as well as interaction with p53 and induction of early apoptotic events. Notably, we found that the acetylation of a single lysine residue coordinates diverse acetylation-dependent processes. Our data provide an example of the complex roles of acetylation as a posttranslational modification that orchestrates the regulation of enzymatic activity, posttranslational modifications, and apoptotic signaling.

Acetylation-dependent coupling between G6PD activity and apoptotic signaling.,Wu F, Muskat NH, Dvilansky I, Koren O, Shahar A, Gazit R, Elia N, Arbely E Nat Commun. 2023 Oct 5;14(1):6208. doi: 10.1038/s41467-023-41895-2. PMID:37798264<ref>PMID:37798264</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zve" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arbely E]]
[[Category: Muskat NH]]
[[Category: Shahar A]]
[[Category: Wu F]]