7n7o - Revision history

OCA at 15:22, 4 October 2023

OCA — Wed, 04 Oct 2023 15:22:17 GMT

←Older revision		Revision as of 15:22, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='7n7o' size='340' side='right'caption='[[7n7o]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='7n7o' size='340' side='right'caption='[[7n7o]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7n7o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N7O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7n7o]] is a 1 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=7N7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N7O FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LQQ:6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>LQQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.7Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIP4K2A, PI5P4KA, PIP5K2, PIP5K2A ([https://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=LQQ:6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>LQQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/1-phosphatidylinositol-5-phosphate_4-kinase 1-phosphatidylinositol-5-phosphate 4-kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.149 2.7.1.149] </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=7n7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n7o OCA], [https://pdbe.org/7n7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n7o RCSB], [https://www.ebi.ac.uk/pdbsum/7n7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n7o ProSAT]</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=7n7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n7o OCA], [https://pdbe.org/7n7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n7o RCSB], [https://www.ebi.ac.uk/pdbsum/7n7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n7o ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/PI42A_HUMAN PI42A_HUMAN]] Precursor B-cell acute lymphoblastic leukemia.	+	[https://www.uniprot.org/uniprot/PI42A_HUMAN PI42A_HUMAN] Precursor B-cell acute lymphoblastic leukemia.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PI42A_HUMAN PI42A_HUMAN]] Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2. May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation. May negatively regulate insulin-stimulated glucose uptake by lowering the levels of PtdIns5P. May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size.<ref>PMID:18364242</ref>	+	[https://www.uniprot.org/uniprot/PI42A_HUMAN PI42A_HUMAN] Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2. May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation. May negatively regulate insulin-stimulated glucose uptake by lowering the levels of PtdIns5P. May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size.<ref>PMID:18364242</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~1-phosphatidylinositol-5-phosphate 4-kinase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen, S]]	+	[[Category: Chen S]]
-	[[Category: Ha, Y]]	+	[[Category: Ha Y]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 10:57, 28 July 2021

OCA — Wed, 28 Jul 2021 10:57:35 GMT

←Older revision		Revision as of 10:57, 28 July 2021
Line 1:		Line 1:

	==Crystal Structure of PI5P4KIIAlpha complex with Palbociclib==		==Crystal Structure of PI5P4KIIAlpha complex with Palbociclib==
-	<StructureSection load='7n7o' size='340' side='right'caption='[[7n7o]]' scene=''>	+	<StructureSection load='7n7o' size='340' side='right'caption='[[7n7o]], [[Resolution\|resolution]] 2.70Å' 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=7N7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N7O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7n7o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N7O 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=7n7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n7o OCA], [https://pdbe.org/7n7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n7o RCSB], [https://www.ebi.ac.uk/pdbsum/7n7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n7o ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LQQ:6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE'>LQQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIP4K2A, PI5P4KA, PIP5K2, PIP5K2A ([https://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/1-phosphatidylinositol-5-phosphate_4-kinase 1-phosphatidylinositol-5-phosphate 4-kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.149 2.7.1.149] </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=7n7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n7o OCA], [https://pdbe.org/7n7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n7o RCSB], [https://www.ebi.ac.uk/pdbsum/7n7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n7o ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/PI42A_HUMAN PI42A_HUMAN]] Precursor B-cell acute lymphoblastic leukemia.
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/PI42A_HUMAN PI42A_HUMAN]] Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2. May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation. May negatively regulate insulin-stimulated glucose uptake by lowering the levels of PtdIns5P. May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size.<ref>PMID:18364242</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Most human cancer cells harbor loss-of-function mutations in the p53 tumor suppressor gene. Genetic experiments have shown that phosphatidylinositol 5-phosphate 4-kinase alpha and beta (PI5P4Kalpha and PI5P4Kbeta) are essential for the development of late-onset tumors in mice with germline p53 deletion, but the mechanism underlying this acquired dependence remains unclear. PI5P4K has been previously implicated in metabolic regulation. Here, we show that inhibition of PI5P4Kalpha/beta kinase activity by a potent and selective small-molecule probe disrupts cell energy homeostasis, causing AMPK activation and mTORC1 inhibition in a variety of cell types. Feedback through the S6K/insulin receptor substrate (IRS) loop contributes to insulin hypersensitivity and enhanced PI3K signaling in terminally differentiated myotubes. Most significantly, the energy stress induced by PI5P4Kalphabeta inhibition is selectively toxic toward p53-null tumor cells. The chemical probe, and the structural basis for its exquisite specificity, provide a promising platform for further development, which may lead to a novel class of diabetes and cancer drugs.
		+
		+	Pharmacological inhibition of PI5P4Kalpha/beta disrupts cell energy metabolism and selectively kills p53-null tumor cells.,Chen S, Chandra Tjin C, Gao X, Xue Y, Jiao H, Zhang R, Wu M, He Z, Ellman J, Ha Y Proc Natl Acad Sci U S A. 2021 May 25;118(21). pii: 2002486118. doi:, 10.1073/pnas.2002486118. PMID:34001596<ref>PMID:34001596</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7n7o" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 1-phosphatidylinositol-5-phosphate 4-kinase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen S]]	+	[[Category: Chen, S]]
-	[[Category: Ha Y]]	+	[[Category: Ha, Y]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 03:34, 2 July 2021

OCA — Fri, 02 Jul 2021 03:34:48 GMT

←Older revision		Revision as of 03:34, 2 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7n7o ~~is ON HOLD~~	+	==Crystal Structure of PI5P4KIIAlpha complex with Palbociclib==
-		+	<StructureSection load='7n7o' size='340' side='right'caption='[[7n7o]]' scene=''>
-	~~Authors~~: ~~Chen~~, S., Ha, Y.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N7O FirstGlance]. <br>
-	~~Description: Crystal Structure of PI5P4KIIAlpha complex with Palbociclib~~	+	</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=7n7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n7o OCA], [https://pdbe.org/7n7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n7o RCSB], [https://www.ebi.ac.uk/pdbsum/7n7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n7o ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Chen, S]]	+	__TOC__
-	[[Category: Ha, Y]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chen S]]
		+	[[Category: Ha Y]]

OCA: Protected "7n7o" [edit=sysop:move=sysop]

OCA — Thu, 17 Jun 2021 13:43:09 GMT

Protected "7n7o" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:43, 17 June 2021

OCA: New page: '''Unreleased structure''' The entry 7n7o is ON HOLD Authors: Chen, S., Ha, Y. Description: Crystal Structure of PI5P4KIIAlpha complex with Palbociclib [[Category: Unreleased Structure...

OCA — Thu, 17 Jun 2021 13:43:08 GMT

New page: '''Unreleased structure''' The entry 7n7o is ON HOLD Authors: Chen, S., Ha, Y. Description: Crystal Structure of PI5P4KIIAlpha complex with Palbociclib [[Category: Unreleased Structure...

New page

'''Unreleased structure'''

The entry 7n7o is ON HOLD

Authors: Chen, S., Ha, Y.

Description: Crystal Structure of PI5P4KIIAlpha complex with Palbociclib
[[Category: Unreleased Structures]]
[[Category: Chen, S]]
[[Category: Ha, Y]]