3l13 - Revision history

OCA at 08:28, 6 September 2023

2023-09-06T08:28:22Z

←Older revision		Revision as of 08:28, 6 September 2023
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	==Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors==		==Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors==
-	<StructureSection load='3l13' size='340' side='right' caption='[[3l13]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='3l13' size='340' side='right'caption='[[3l13]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3l13]] is a 1 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3L13 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3l13]] 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L13 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</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]] 3Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l16\|3l16]]~~, [[~~3l17~~\|~~3l17~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PIK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [https://pdbe.org/3l13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [https://www.ebi.ac.uk/pdbsum/3l13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l13 ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~http://en.wikipedia.org/wiki/Phosphatidylinositol~~-4,5-~~bisphosphate_3~~-~~kinase Phosphatidylinositol~~-4,5-~~bisphosphate~~ 3-~~kinase~~]~~, with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2~~.7.1.153 2.7.1.153~~] </~~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=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [~~http~~://pdbe.org/3l13 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3l13 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3l13 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>	+	[https://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l1/3l13_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l1/3l13_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	</div>		</div>
	<div class="pdbe-citations 3l13" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3l13" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Phosphatidylinositol-4,5-bisphosphate 3-kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Murray~~, J M~~]]	+	[[Category: Murray JM]]
-	[[Category: Wiesmann, C]]	+	[[Category: Wiesmann C]]
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Pi3k-gamma p110 gamma]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:45, 1 November 2017

2017-11-01T08:45:52Z

←Older revision		Revision as of 08:45, 1 November 2017
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3l13" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3l13" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:47, 5 August 2016

2016-08-05T20:47:33Z

←Older revision		Revision as of 20:47, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors==		==Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors==
	<StructureSection load='3l13' size='340' side='right' caption='[[3l13]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='3l13' size='340' side='right' caption='[[3l13]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3l13]] is a 1 chain structure with sequence 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L13 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3l13]] is a 1 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L13 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l16\|3l16]], [[3l17\|3l17]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l16\|3l16]], [[3l17\|3l17]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG ([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/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </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=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [http://www.ebi.ac.uk/pdbsum/3l13 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=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [http://pdbe.org/3l13 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [http://www.ebi.ac.uk/pdbsum/3l13 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l13 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</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=3l13 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	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 3l13" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Murray, J M]]		[[Category: Murray, J M]]

OCA at 21:47, 25 December 2014

2014-12-25T21:47:33Z

←Older revision		Revision as of 21:47, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3l13]] is a 1 chain structure with sequence 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L13 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3l13]] is a 1 chain structure with sequence 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L13 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l16\|3l16]], [[3l17\|3l17]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l16\|3l16]], [[3l17\|3l17]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [http://www.ebi.ac.uk/pdbsum/3l13 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=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [http://www.ebi.ac.uk/pdbsum/3l13 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
-	[[Category: Murray, J M.]]	+	[[Category: Murray, J M]]
-	[[Category: Wiesmann, C.]]	+	[[Category: Wiesmann, C]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Kinase]]		[[Category: Kinase]]

OCA at 13:33, 29 September 2014

2014-09-29T13:33:23Z

←Older revision		Revision as of 13:33, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~3l13.~~png~~\|~~left~~\|200px]]	+	==Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors==
		+	<StructureSection load='3l13' size='340' side='right' caption='[[3l13]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3l13]] is a 1 chain structure with sequence 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=3L13 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L13 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JZW:[3-(6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL)PHENYL]METHANOL'>JZW</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3l16\|3l16]], [[3l17\|3l17]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l13 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l13 RCSB], [http://www.ebi.ac.uk/pdbsum/3l13 PDBsum]</span></td></tr>
		+	<table>
		+	== 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/l1/3l13_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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The PI3K/AKT/mTOR pathway has been shown to play an important role in cancer. Starting with compounds 1 and 2 (GDC-0941) as templates, (thienopyrimidin-2-yl)aminopyrimidines were discovered as potent inhibitors of PI3K or both PI3K and mTOR. Structural information derived from PI3Kgamma-ligand cocrystal structures of 1 and 2 were used to design inhibitors that maintained potency for PI3K yet improved metabolic stability and oral bioavailability relative to 1. The addition of a single methyl group to the optimized 5 resulted in 21, which had significantly reduced potency for mTOR. The lead compounds 5 (GNE-493) and 21 (GNE-490) have good pharmacokinetic (PK) parameters, are highly selective, demonstrate knock down of pathway markers in vivo, and are efficacious in xenograft models where the PI3K pathway is deregulated. Both compounds were compared in a PI3Kalpha mutated MCF7.1 xenograft model and were found to have equivalent efficacy when normalized for exposure.

-	~~{{STRUCTURE_3l13\| PDB=3l13 \| SCENE= }}~~	+	Discovery of (Thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors for the Treatment of Cancer.,Sutherlin DP, Sampath D, Berry M, Castanedo G, Chang Z, Chuckowree I, Dotson J, Folkes A, Friedman L, Goldsmith R, Heffron T, Lee L, Lesnick J, Lewis C, Mathieu S, Nonomiya J, Olivero A, Pang J, Prior WW, Salphati L, Sideris S, Tian Q, Tsui V, Wan NC, Wang S, Wiesmann C, Wong S, Zhu BY J Med Chem. 2010 Feb 11;53(3):1086-97. PMID:20050669<ref>PMID:20050669</ref>

-	~~===Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase~~/~~mTOR Inhibitors===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20050669}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3l13]] is~~ a ~~1 chain structure with sequence 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=3L13 OCA].~~	+

	==See Also==		==See Also==
	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]		*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020050669<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]

OCA at 22:02, 20 October 2012

2012-10-20T22:02:10Z

←Older revision		Revision as of 22:02, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3l13]] is a 1 chain structure ~~of [[Phosphoinositide 3-Kinases]]~~ with sequence 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=3L13 OCA].	+	[[3l13]] is a 1 chain structure with sequence 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=3L13 OCA].

	==See Also==		==See Also==

OCA: Protected "3l13" [edit=sysop:move=sysop]

2012-07-27T15:02:53Z

Protected "3l13" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:02, 27 July 2012

OCA at 15:02, 27 July 2012

2012-07-27T15:02:51Z

←Older revision		Revision as of 15:02, 27 July 2012
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3l13.png\|left\|200px]]
-	[[Image:3l13.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3l13", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3l13\| PDB=3l13 \| SCENE= }}		{{STRUCTURE_3l13\| PDB=3l13 \| SCENE= }}

	===Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors===		===Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20050669}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20050669 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20050669}}		{{ABSTRACT_PUBMED_20050669}}

	==About this Structure==		==About this Structure==
-	~~3L13~~ is a 1 chain structure with sequence 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=3L13 OCA].	+	[[3l13]] is a 1 chain structure of [[Phosphoinositide 3-Kinases]] with sequence 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=3L13 OCA].
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20050669~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020050669</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
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	[[Category: Pi3k-gamma p110 gamma]]		[[Category: Pi3k-gamma p110 gamma]]
	[[Category: Transferase]]		[[Category: Transferase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 17 10:29:34 2010''

OCA at 08:29, 17 February 2010

2010-02-17T08:29:34Z

←Older revision		Revision as of 08:29, 17 February 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3l13.jpg\|left\|200px]]

-	The ~~entry 3l13~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3l13", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3l13\| PDB=3l13 \| SCENE= }}

-	~~Authors: Murray, J.M., Wiesmann, C.~~	+	===Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors===

-	Description: Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 10 16:57:12 2010''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20050669}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20050669 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20050669}}
		+
		+	==About this Structure==
		+	3L13 is a 1 chain structure with sequence 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=3L13 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20050669</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
		+	[[Category: Murray, J M.]]
		+	[[Category: Wiesmann, C.]]
		+	[[Category: Atp-binding]]
		+	[[Category: Kinase]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Pi3k-gamma p110 gamma]]
		+	[[Category: Transferase]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 17 10:29:34 2010''

OCA at 14:57, 10 February 2010

2010-02-10T14:57:13Z

←Older revision		Revision as of 14:57, 10 February 2010
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3l13 is ON HOLD	+	The entry 3l13 is ON HOLD until Paper Publication

	Authors: Murray, J.M., Wiesmann, C.		Authors: Murray, J.M., Wiesmann, C.
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	Description: Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors		Description: Crystal Structures of Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Dec 23 09~~:25:~~23 2009~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 10 16:57:12 2010''