4g1n

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==PKM2 in complex with an activator==
==PKM2 in complex with an activator==
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<StructureSection load='4g1n' size='340' side='right' caption='[[4g1n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='4g1n' size='340' side='right'caption='[[4g1n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4g1n]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G1N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G1N FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4g1n]] 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=4G1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G1N FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NZT:N-(4-{[4-(PYRAZIN-2-YL)PIPERAZIN-1-YL]CARBONYL}PHENYL)QUINOLINE-8-SULFONAMIDE'>NZT</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKM2, OIP3, PK2, PK3, PKM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NZT:N-(4-{[4-(PYRAZIN-2-YL)PIPERAZIN-1-YL]CARBONYL}PHENYL)QUINOLINE-8-SULFONAMIDE'>NZT</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4g1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g1n OCA], [https://pdbe.org/4g1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g1n RCSB], [https://www.ebi.ac.uk/pdbsum/4g1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g1n ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4g1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g1n OCA], [http://pdbe.org/4g1n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g1n RCSB], [http://www.ebi.ac.uk/pdbsum/4g1n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g1n ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://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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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM2 isoform, effectively constraining lower glycolysis. Here, we report the discovery of PKM2 activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM2 activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the nonessential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress.
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Small Molecule Activation of PKM2 in Cancer Cells Induces Serine Auxotrophy.,Kung C, Hixon J, Choe S, Marks K, Gross S, Murphy E, Delabarre B, Cianchetta G, Sethumadhavan S, Wang X, Yan S, Gao Y, Fang C, Wei W, Jiang F, Wang S, Qian K, Saunders J, Driggers E, Woo HK, Kunii K, Murray S, Yang H, Yen K, Liu W, Cantley LC, Vander Heiden MG, Su SM, Jin S, Salituro FG, Dang L Chem Biol. 2012 Sep 21;19(9):1187-98. doi: 10.1016/j.chembiol.2012.07.021. PMID:22999886<ref>PMID:22999886</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4g1n" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Pyruvate Kinase|Pyruvate Kinase]]
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*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Pyruvate kinase]]
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[[Category: Large Structures]]
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[[Category: Dang, L]]
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[[Category: Dang L]]
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[[Category: DeLaBarre, B]]
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[[Category: DeLaBarre B]]
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[[Category: Hixon, J]]
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[[Category: Hixon J]]
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[[Category: Kung, C]]
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[[Category: Kung C]]
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[[Category: Qian, K C]]
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[[Category: Qian KC]]
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[[Category: Activator]]
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[[Category: Aerobic glycolysis]]
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[[Category: Cancer metabolism]]
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[[Category: Phosphorylation of pyruvate]]
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[[Category: Transferase-activator complex]]
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Current revision

PKM2 in complex with an activator

PDB ID 4g1n

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