4qg8 - Revision history

OCA at 19:24, 29 May 2024

OCA — Wed, 29 May 2024 19:24:35 GMT

←Older revision		Revision as of 19:24, 29 May 2024
Line 1:		Line 1:

	==crystal structure of PKM2-K305Q mutant==		==crystal structure of PKM2-K305Q mutant==
-	<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]]' scene=''>	+	<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qg8]] 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=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>
-	</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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [https://pdbe.org/4qg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 ProSAT]</span></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]] 2.3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [https://pdbe.org/4qg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 ProSAT]</span></td></tr>
	</table>		</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a "seesaw" model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2Y105E (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2K305Q (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.
		+
		+	Structural insight into mechanisms for dynamic regulation of PKM2.,Wang P, Sun C, Zhu T, Xu Y Protein Cell. 2015 Feb 4. PMID:25645022<ref>PMID:25645022</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4qg8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]		*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sun C]]		[[Category: Sun C]]

OCA at 10:54, 31 August 2022

OCA — Wed, 31 Aug 2022 10:54:48 GMT

←Older revision		Revision as of 10:54, 31 August 2022
Line 1:		Line 1:

	==crystal structure of PKM2-K305Q mutant==		==crystal structure of PKM2-K305Q mutant==
-	<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]]~~, [[Resolution\|resolution]] 2.30Å~~' scene=''>	+	<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[4qg8]] is a 4 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>	+	</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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [https://pdbe.org/4qg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</div></td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [https://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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [https://pdbe.org/4qg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 ProSAT]</span></td></tr>	+
	</table>		</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>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a "seesaw" model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2Y105E (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2K305Q (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.
-
-	Structural insight into mechanisms for dynamic regulation of PKM2.,Wang P, Sun C, Zhu T, Xu Y Protein Cell. 2015 Feb 4. PMID:25645022<ref>PMID:25645022</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4qg8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]		*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Pyruvate kinase]]~~	+	[[Category: Sun C]]
-	[[Category: Sun, C]]	+	[[Category: Wang P]]
-	[[Category: Wang, P]]	+	[[Category: Xu Y]]
-	[[Category: Xu, Y]]	+	[[Category: Zhu T]]
-	[[Category: Zhu, T]]	+
-	~~[[Category: Tetramer]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:06, 25 August 2022

OCA — Thu, 25 Aug 2022 05:06:55 GMT

←Older revision		Revision as of 05:06, 25 August 2022
Line 3:		Line 3:
	<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qg8]] 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=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qg8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</td>~~</tr>~~	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</div></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'>[https://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span></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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [https://pdbe.org/4qg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [~~http~~://pdbe.org/4qg8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:

	==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: Large Structures]]		[[Category: Large Structures]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]

OCA at 09:22, 24 April 2019

OCA — Wed, 24 Apr 2019 09:22:49 GMT

←Older revision		Revision as of 09:22, 24 April 2019
Line 1:		Line 1:

	==crystal structure of PKM2-K305Q mutant==		==crystal structure of PKM2-K305Q mutant==
-	<StructureSection load='4qg8' size='340' side='right' caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4qg8' size='340' side='right'caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qg8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qg8]] 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=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</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='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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [http://pdbe.org/4qg8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [http://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [http://pdbe.org/4qg8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [http://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 ProSAT]</span></td></tr>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]
	[[Category: Sun, C]]		[[Category: Sun, C]]

OCA at 17:06, 4 January 2017

OCA — Wed, 04 Jan 2017 17:06:19 GMT

←Older revision		Revision as of 17:06, 4 January 2017
Line 1:		Line 1:
		+
	==crystal structure of PKM2-K305Q mutant==		==crystal structure of PKM2-K305Q mutant==
	<StructureSection load='4qg8' size='340' side='right' caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4qg8' size='340' side='right' caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</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='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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [http://www.ebi.ac.uk/pdbsum/4qg8 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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [http://pdbe.org/4qg8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [http://www.ebi.ac.uk/pdbsum/4qg8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qg8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4qg8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pyruvate Kinase\|Pyruvate Kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:38, 26 March 2015

OCA — Thu, 26 Mar 2015 07:38:23 GMT

←Older revision		Revision as of 07:38, 26 March 2015
Line 1:		Line 1:
-	==~~Crystal~~ structure of PKM2 mutant 2==	+	==crystal structure of PKM2-K305Q mutant==
	<StructureSection load='4qg8' size='340' side='right' caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4qg8' size='340' side='right' caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 13:52, 25 February 2015

OCA — Wed, 25 Feb 2015 13:52:17 GMT

←Older revision		Revision as of 13:52, 25 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of PKM2 mutant 2==
		+	<StructureSection load='4qg8' size='340' side='right' caption='[[4qg8]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4qg8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QG8 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rpp\|4rpp]], [[4qgc\|4qgc]], [[4qg9\|4qg9]], [[4qg6\|4qg6]]</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=4qg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qg8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qg8 RCSB], [http://www.ebi.ac.uk/pdbsum/4qg8 PDBsum]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a "seesaw" model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2Y105E (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2K305Q (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.

-	~~The entry 4qg8 is ON HOLD until Paper Publication~~	+	Structural insight into mechanisms for dynamic regulation of PKM2.,Wang P, Sun C, Zhu T, Xu Y Protein Cell. 2015 Feb 4. PMID:25645022<ref>PMID:25645022</ref>

-	~~Authors: Wang~~, P.~~, Sun, C~~.~~, Zhu, T., Xu, Y~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of PKM2 mutant 2~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Pyruvate kinase]]
		+	[[Category: Sun, C]]
		+	[[Category: Wang, P]]
	[[Category: Xu, Y]]		[[Category: Xu, Y]]
-	[[Category: Sun, C]]
	[[Category: Zhu, T]]		[[Category: Zhu, T]]
-	[[Category: ~~Wang, P~~]]	+	[[Category: Tetramer]]
		+	[[Category: Transferase]]

OCA at 15:46, 24 December 2014

OCA — Wed, 24 Dec 2014 15:46:11 GMT

←Older revision		Revision as of 15:46, 24 December 2014
Line 6:		Line 6:

	Description: Crystal structure of PKM2 mutant 2		Description: Crystal structure of PKM2 mutant 2
		+	[[Category: Unreleased Structures]]
		+	[[Category: Xu, Y]]
		+	[[Category: Sun, C]]
		+	[[Category: Zhu, T]]
		+	[[Category: Wang, P]]

OCA at 06:36, 18 June 2014

OCA — Wed, 18 Jun 2014 06:36:23 GMT

←Older revision		Revision as of 06:36, 18 June 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4qg8 is ON HOLD	+	The entry 4qg8 is ON HOLD until Paper Publication

	Authors: Wang, P., Sun, C., Zhu, T., Xu, Y.		Authors: Wang, P., Sun, C., Zhu, T., Xu, Y.

	Description: Crystal structure of PKM2 mutant 2		Description: Crystal structure of PKM2 mutant 2

OCA at 08:05, 11 June 2014

OCA — Wed, 11 Jun 2014 08:05:08 GMT

←Older revision		Revision as of 08:05, 11 June 2014
Line 3:		Line 3:
	The entry 4qg8 is ON HOLD		The entry 4qg8 is ON HOLD

-	Authors: ~~Ping~~ Wang, ~~Chang~~ Sun, ~~Tingting~~ Zhu, ~~Yanhui~~ Xu	+	Authors: Wang, P., Sun, C., Zhu, T., Xu, Y.

	Description: Crystal structure of PKM2 mutant 2		Description: Crystal structure of PKM2 mutant 2