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6b6u

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Revision as of 06:03, 3 January 2018

Pyruvate Kinase M2 mutant - S437Y

Structural highlights

6b6u is a 2 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:	PKM, OIP3, PK2, PK3, PKM2 (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

Pyruvate kinase muscle isoform 2 (PKM2) catalyzes the terminal step in glycolysis, transferring a phosphoryl group from phosphoenolpyruvate to ADP, to produce pyruvate and ATP. PKM2 activity is allosterically regulated by fructose 1,6-bisphosphate (FBP), an upstream glycolytic intermediate. FBP stabilizes the tetrameric form of the enzyme. In its absence, the PKM2 tetramers dissociate, yielding a dimer-monomer mixture having lower enzymatic activity. The S437Y variant of PKM2 is incapable of binding FBP. Consistent with that defect, we find that S437Y exists in a monomer-dimer equilibrium in solution, with a Kd of approximately 20 muM. Interestingly, however, the protein crystallizes as a tetramer, providing insight into the structural basis for impaired FBP binding of S437Y.

Structural Investigation of a Dimeric Variant of Pyruvate Kinase Muscle Isoform 2.,Srivastava D, Razzaghi M, Henzl MT, Dey M Biochemistry. 2017 Dec 19;56(50):6517-6520. doi: 10.1021/acs.biochem.7b01013., Epub 2017 Dec 1. PMID:29182273^[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
↑ Srivastava D, Razzaghi M, Henzl MT, Dey M. Structural Investigation of a Dimeric Variant of Pyruvate Kinase Muscle Isoform 2. Biochemistry. 2017 Dec 19;56(50):6517-6520. doi: 10.1021/acs.biochem.7b01013., Epub 2017 Dec 1. PMID:29182273 doi:http://dx.doi.org/10.1021/acs.biochem.7b01013

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6b6u"

@@ Line 3: / Line 3: @@
 <StructureSection load='6b6u' size='340' side='right' caption='[[6b6u]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b6u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B6U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b6u]] is a 2 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=6B6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B6U FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKM, OIP3, PK2, PK3, PKM2 ([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=6b6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b6u OCA], [http://pdbe.org/6b6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b6u RCSB], [http://www.ebi.ac.uk/pdbsum/6b6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b6u ProSAT]</span></td></tr>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Pyruvate kinase]]
 [[Category: Dey, M]]

6b6u

From Proteopedia

Revision as of 06:03, 3 January 2018

Pyruvate Kinase M2 mutant - S437Y

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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