4b2d

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[[Image:4b2d.png|left|200px]]
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==human PKM2 with L-serine and FBP bound.==
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<StructureSection load='4b2d' size='340' side='right' caption='[[4b2d]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4b2d]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B2D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B2D 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=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SER:SERINE'>SER</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1t5a|1t5a]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4b2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b2d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b2d RCSB], [http://www.ebi.ac.uk/pdbsum/4b2d PDBsum]</span></td></tr>
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</table>
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== 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.
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{{STRUCTURE_4b2d| PDB=4b2d | SCENE= }}
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Serine is a natural ligand and allosteric activator of pyruvate kinase M2.,Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M, Gottlieb E Nature. 2012 Oct 14. doi: 10.1038/nature11540. PMID:23064226<ref>PMID:23064226</ref>
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===human PKM2 with L-serine and FBP bound.===
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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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{{ABSTRACT_PUBMED_23064226}}
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==See Also==
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*[[Pyruvate Kinase|Pyruvate Kinase]]
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==About this Structure==
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== References ==
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[[4b2d]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B2D OCA].
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Pyruvate kinase]]
[[Category: Pyruvate kinase]]
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[[Category: Chaneton, B.]]
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[[Category: Chaneton, B]]
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[[Category: Chokkathukalam, A.]]
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[[Category: Chokkathukalam, A]]
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[[Category: Coyle, J E.]]
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[[Category: Coyle, J E]]
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[[Category: Frezza, C.]]
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[[Category: Frezza, C]]
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[[Category: Gottlieb, E.]]
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[[Category: Gottlieb, E]]
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[[Category: Hillmann, P.]]
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[[Category: Hillmann, P]]
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[[Category: Holding, F P.]]
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[[Category: Holding, F P]]
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[[Category: Jankevics, A.]]
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[[Category: Jankevics, A]]
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[[Category: Maddocks, O D.K.]]
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[[Category: Maddocks, O D.K]]
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[[Category: Martin, A C.L.]]
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[[Category: Martin, A C.L]]
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[[Category: OReilly, M.]]
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[[Category: OReilly, M]]
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[[Category: Vousden, K H.]]
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[[Category: Vousden, K H]]
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[[Category: Zheng, L.]]
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[[Category: Zheng, L]]
[[Category: Glycolysis]]
[[Category: Glycolysis]]
[[Category: Pkm2]]
[[Category: Pkm2]]
[[Category: Transferase]]
[[Category: Transferase]]
[[Category: Tumour]]
[[Category: Tumour]]

Revision as of 00:29, 25 December 2014

human PKM2 with L-serine and FBP bound.

4b2d, resolution 2.30Å

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