4qg6

<StructureSection load='4qg6' size='340' side='right'caption='[[4qg6]], [[Resolution|resolution]] 3.21&Aring;' scene=''>

<table><tr><td colspan='2'>[[4qg6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QG6 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PRO:PROLINE'>PRO</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=4qg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg6 OCA], [https://pdbe.org/4qg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qg6 RCSB], [https://www.ebi.ac.uk/pdbsum/4qg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg6 ProSAT]</span></td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/KPYM_HUMAN KPYM_HUMAN]] Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.<ref>PMID:17308100</ref> <ref>PMID:18191611</ref> <ref>PMID:21620138</ref>

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== Publication Abstract from PubMed ==

Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a "seesaw" model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2Y105E (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2K305Q (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.

Structural insight into mechanisms for dynamic regulation of PKM2.,Wang P, Sun C, Zhu T, Xu Y Protein Cell. 2015 Feb 4. PMID:25645022<ref>PMID:25645022</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 4qg6" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Sun, C]]

[[Category: Wang, P]]

[[Category: Xu, Y]]

[[Category: Zhu, T]]

[[Category: Transferase]]