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4g1n

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Revision as of 11:19, 5 August 2016

PKM2 in complex with an activator

Structural highlights

4g1n is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	PKM2, OIP3, PK2, PK3, PKM (HUMAN)
Activity:	Pyruvate kinase, with EC number 2.7.1.40
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Stetak A, Veress R, Ovadi J, Csermely P, Keri G, Ullrich A. Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res. 2007 Feb 15;67(4):1602-8. PMID:17308100 doi:10.1158/0008-5472.CAN-06-2870
↑ Lee J, Kim HK, Han YM, Kim J. Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. Int J Biochem Cell Biol. 2008;40(5):1043-54. doi: 10.1016/j.biocel.2007.11.009., Epub 2007 Nov 29. PMID:18191611 doi:10.1016/j.biocel.2007.11.009
↑ Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, Cole RN, Pandey A, Semenza GL. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011 May 27;145(5):732-44. doi: 10.1016/j.cell.2011.03.054. PMID:21620138 doi:10.1016/j.cell.2011.03.054
↑ 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. Small Molecule Activation of PKM2 in Cancer Cells Induces Serine Auxotrophy. Chem Biol. 2012 Sep 21;19(9):1187-98. doi: 10.1016/j.chembiol.2012.07.021. PMID:22999886 doi:http://dx.doi.org/10.1016/j.chembiol.2012.07.021

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4g1n"

@@ Line 1: / Line 1: @@
 ==PKM2 in complex with an activator==
 <StructureSection load='4g1n' size='340' side='right' caption='[[4g1n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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>
 <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>
-<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://www.rcsb.org/pdb/explore.do?structureId=4g1n RCSB], [http://www.ebi.ac.uk/pdbsum/4g1n PDBsum]</span></td></tr>
+<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>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4g1n" style="background-color:#fffaf0;"></div>
 ==See Also==

4g1n

From Proteopedia

Revision as of 11:19, 5 August 2016

PKM2 in complex with an activator

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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