View source for 7qqh


==Crystal structure of MYORG (D520N) in complex with Gal-a1,4-Glc==
<StructureSection load='7qqh' size='340' side='right'caption='[[7qqh]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qqh]] is a 4 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=7QQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QQH 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=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLA:ALPHA+D-GALACTOSE'>GLA</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7qqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qqh OCA], [https://pdbe.org/7qqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qqh RCSB], [https://www.ebi.ac.uk/pdbsum/7qqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qqh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MYORG_HUMAN MYORG_HUMAN] Bilateral striopallidodentate calcinosis. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MYORG_HUMAN MYORG_HUMAN] Putative glycosidase. Promotes myogenesis by activating AKT signaling through the maturation and secretion of IGF2.[UniProtKB:Q69ZQ1]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Primary familial brain calcification (PFBC) is characterised by abnormal deposits of calcium phosphate within various regions of the brain that are associated with severe cognitive impairments, psychiatric conditions, and movement disorders. Recent studies in diverse populations have shown a link between mutations in myogenesis-regulating glycosidase (MYORG) and the development of this disease. MYORG is a member of glycoside hydrolase (GH) family 31 (GH31) and, like the other mammalian GH31 enzyme alpha-glucosidase II, this enzyme is found in the lumen of the endoplasmic reticulum (ER). Though presumed to act as an alpha-glucosidase due to its localization and sequence relatedness to alpha-glucosidase II, MYORG has never been shown to exhibit catalytic activity. Here, we show that MYORG is an alpha-galactosidase and present the high-resolution crystal structure of MYORG in complex with substrate and inhibitor. Using these structures, we map detrimental mutations that are associated with MYORG-associated brain calcification and define how these mutations may drive disease progression through loss of enzymatic activity. Finally, we also detail the thermal stabilisation of MYORG afforded by a clinically approved small molecule ligand, opening the possibility of using pharmacological chaperones to enhance the activity of mutant forms of MYORG.

The primary familial brain calcification-associated protein MYORG is an alpha-galactosidase with restricted substrate specificity.,Meek RW, Brockerman J, Fordwour OB, Zandberg WF, Davies GJ, Vocadlo DJ PLoS Biol. 2022 Sep 21;20(9):e3001764. doi: 10.1371/journal.pbio.3001764. , eCollection 2022 Sep. PMID:36129849<ref>PMID:36129849</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qqh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Davies GJ]]
[[Category: Meek RW]]