3u2z

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:47, 14 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
==Activator-Bound Structure of Human Pyruvate Kinase M2==
==Activator-Bound Structure of Human Pyruvate Kinase M2==
-
<StructureSection load='3u2z' size='340' side='right' caption='[[3u2z]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+
<StructureSection load='3u2z' size='340' side='right'caption='[[3u2z]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[3u2z]] 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=3U2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U2Z FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[3u2z]] 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=3U2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U2Z FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07T:6-(3-AMINOBENZYL)-4-METHYL-2-METHYLSULFINYL-4,6-DIHYDRO-5H-THIENO[2,3 4,5]PYRROLO[2,3-D]PYRIDAZIN-5-ONE'>07T</scene>, <scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
-
<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=07T:6-(3-AMINOBENZYL)-4-METHYL-2-METHYLSULFINYL-4,6-DIHYDRO-5H-THIENO[2,3 4,5]PYRROLO[2,3-D]PYRIDAZIN-5-ONE'>07T</scene>, <scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3u2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u2z OCA], [https://pdbe.org/3u2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u2z RCSB], [https://www.ebi.ac.uk/pdbsum/3u2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u2z ProSAT]</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=3u2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u2z OCA], [http://pdbe.org/3u2z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u2z RCSB], [http://www.ebi.ac.uk/pdbsum/3u2z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u2z ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[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>
+
[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>
-
<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.
+
-
 
+
-
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 3u2z" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
-
*[[Pyruvate Kinase|Pyruvate Kinase]]
+
*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
-
[[Category: Pyruvate kinase]]
+
[[Category: Large Structures]]
-
[[Category: Arrowsmith, C H]]
+
[[Category: Arrowsmith CH]]
-
[[Category: Auld, D]]
+
[[Category: Auld D]]
-
[[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: Structural genomic]]
+
[[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: Sgc]]
+
-
[[Category: Transferase]]
+
-
[[Category: Transferase-transferase activator complex]]
+

Current revision

Activator-Bound Structure of Human Pyruvate Kinase M2

PDB ID 3u2z

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3u2z"
Personal tools