View source for 7q0b


==Human GYS1-GYG1 complex inhibited state==
<StructureSection load='7q0b' size='340' side='right'caption='[[7q0b]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7q0b]] 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=7Q0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q0B 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7q0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q0b OCA], [https://pdbe.org/7q0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q0b RCSB], [https://www.ebi.ac.uk/pdbsum/7q0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q0b ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GYS1_HUMAN GYS1_HUMAN] Glycogen storage disease due to muscle and heart glycogen synthase deficiency. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GYS1_HUMAN GYS1_HUMAN] Glycogen synthase participates in the glycogen biosynthetic process along with glycogenin and glycogen branching enzyme. Extends the primer composed of a few glucose units formed by glycogenin by adding new glucose units to it. In this context, glycogen synthase transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan.<ref>PMID:35835870</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glycogen synthase (GYS1) is the central enzyme in muscle glycogen biosynthesis. GYS1 activity is inhibited by phosphorylation of its amino (N) and carboxyl (C) termini, which is relieved by allosteric activation of glucose-6-phosphate (Glc6P). We present cryo-EM structures at 3.0-4.0 A resolution of phosphorylated human GYS1, in complex with a minimal interacting region of glycogenin, in the inhibited, activated and catalytically competent states. Phosphorylations of specific terminal residues are sensed by different arginine clusters, locking the GYS1 tetramer in an inhibited state via intersubunit interactions. The Glc6P activator promotes conformational change by disrupting these interactions and increases the flexibility of GYS1, such that it is poised to adopt a catalytically competent state when the sugar donor UDP-glucose (UDP-glc) binds. We also identify an inhibited-like conformation that has not transitioned into the activated state, in which the locking interaction of phosphorylation with the arginine cluster impedes subsequent conformational changes due to Glc6P binding. Our results address longstanding questions regarding the mechanism of human GYS1 regulation.

Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.,McCorvie TJ, Loria PM, Tu M, Han S, Shrestha L, Froese DS, Ferreira IM, Berg AP, Yue WW Nat Struct Mol Biol. 2022 Jul;29(7):628-638. doi: 10.1038/s41594-022-00799-3. , Epub 2022 Jul 14. PMID:35835870<ref>PMID:35835870</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7q0b" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glycogenin|Glycogenin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ferreira IM]]
[[Category: Froese DS]]
[[Category: McCorvie TJ]]
[[Category: Shrestha L]]
[[Category: Yue WW]]