3me3: Difference between revisions

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-{{Seed}}
-[[Image:3me3.jpg|left|200px]]
-<!--
+==Activator-Bound Structure of Human Pyruvate Kinase M2==
-The line below this paragraph, containing "STRUCTURE_3me3", creates the "Structure Box" on the page.
+<StructureSection load='3me3' size='340' side='right'caption='[[3me3]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3me3]] 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=3ME3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ME3 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3SZ:3-{[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YLSULFONYL)-1,4-DIAZEPAN-1-YL]SULFONYL}ANILINE'>3SZ</scene>, <scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
-{{STRUCTURE_3me3|  PDB=3me3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3me3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3me3 OCA], [https://pdbe.org/3me3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3me3 RCSB], [https://www.ebi.ac.uk/pdbsum/3me3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3me3 ProSAT]</span></td></tr>
+</table>
+== 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/me/3me3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3me3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.
-===Activator-Bound Structure of Human Pyruvate Kinase M2===
+Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis.,Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, Yang H, Mattaini KR, Metallo CM, Fiske BP, Courtney KD, Malstrom S, Khan TM, Kung C, Skoumbourdis AP, Veith H, Southall N, Walsh MJ, Brimacombe KR, Leister W, Lunt SY, Johnson ZR, Yen KE, Kunii K, Davidson SM, Christofk HR, Austin CP, Inglese J, Harris MH, Asara JM, Stephanopoulos G, Salituro FG, Jin S, Dang L, Auld DS, Park HW, Cantley LC, Thomas CJ, Heiden MG Nat Chem Biol. 2012 Aug 26. doi: 10.1038/nchembio.1060. PMID:22922757<ref>PMID:22922757</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3me3" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-ME3 is a 4 chains structure with sequences 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=3ME3 OCA].
+*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Pyruvate kinase]]
+[[Category: Large Structures]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith CH]]
-[[Category: Auld, D.]]
+[[Category: Auld D]]
-[[Category: Bochkarev, A.]]
+[[Category: Bochkarev A]]
-[[Category: Bountra, C.]]
+[[Category: Bountra C]]
-[[Category: Boxer, M.]]
+[[Category: Boxer M]]
-[[Category: Dimov, S.]]
+[[Category: Dimov S]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards AM]]
-[[Category: Hong, B.]]
+[[Category: Hong B]]
-[[Category: Inglese, J.]]
+[[Category: Inglese J]]
-[[Category: Jianq, J K.]]
+[[Category: Jianq J-K]]
-[[Category: Min, S.]]
+[[Category: Min S]]
-[[Category: Park, H.]]
+[[Category: Park H]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Skoumbourdis A]]
-[[Category: Skoumbourdis, A.]]
+[[Category: Southall N]]
-[[Category: Southall, N.]]
+[[Category: Tempel W]]
-[[Category: Tempel, W.]]
+[[Category: Thomas C]]
-[[Category: Thomas, C.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
-[[Category: Activator]]
-[[Category: Sgc]]
-[[Category: Structural genomics consortium]]
-[[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 28 11:10:02 2010''