4ps3 - Revision history

OCA at 12:42, 1 March 2024

2024-03-01T12:42:48Z

← Older revision		Revision as of 12:42, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ps3]] 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=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ps3]] 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=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</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]] 2.9Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [https://pdbe.org/4ps3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [https://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [https://pdbe.org/4ps3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [https://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[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>		[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>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Phosphoinositide 3-kinase gamma (PI3Kgamma) is an attractive target to potentially treat a range of disease states. Herein, we describe the evolution of a reported phenylthiazole pan-PI3K inhibitor into a family of potent and selective benzothiazole inhibitors. Using X-ray crystallography, we discovered that compound 22 occupies a previously unreported hydrophobic binding cleft adjacent to the ATP binding site of PI3Kgamma, and achieves its selectivity by exploiting natural sequence differences among PI3K isoforms in this region.

	Structural Basis for Isoform Selectivity in a Class of Benzothiazole Inhibitors of Phosphoinositide 3-Kinase gamma,Collier PN, Martinez-Botella G, Cornebise M, Cottrell KM, Doran JD, Griffith JP, Mahajan S, Maltais F, Moody CS, Huck EP, Wang T, Aronov AM J Med Chem. 2014 May 2. PMID:24754609<ref>PMID:24754609</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4ps3" style="background-color:#fffaf0;"></div>~~

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

OCA at 07:27, 8 February 2023

2023-02-08T07:27:43Z

← Older revision		Revision as of 07:27, 8 February 2023
Line 3:		Line 3:
	<StructureSection load='4ps3' size='340' side='right'caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='4ps3' size='340' side='right'caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ps3]] 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=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ps3]] 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=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [https://pdbe.org/4ps3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [https://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PI3K gamma, 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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [~~http~~://pdbe.org/4ps3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Phosphoinositide 3-~~Kinases~~\|Phosphoinositide 3-~~Kinases~~]]		*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Griffith~~, J P]]~~		[[Category: Griffith JP]]
	~~[[Category: Serine/threonine protein kinase]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 07:53, 17 April 2019

2019-04-17T07:53:55Z

← Older revision		Revision as of 07:53, 17 April 2019
Line 1:		Line 1:

	==Structure of PI3K gamma in complex with 1-[6-(5-methoxypyridin-3-yl)-1,3-benzothiazol-2-yl]-3-[2-(1-propyl-1H-imidazol-4-yl)ethyl]urea==		==Structure of PI3K gamma in complex with 1-[6-(5-methoxypyridin-3-yl)-1,3-benzothiazol-2-yl]-3-[2-(1-propyl-1H-imidazol-4-yl)ethyl]urea==
	<StructureSection load='4ps3' size='340' side='right' caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='4ps3' size='340' side='right'caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ps3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ps3]] 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=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PI3K gamma, 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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [http://pdbe.org/4ps3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [http://pdbe.org/4ps3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 ProSAT]</span></td></tr>
	</table>		</table>
Line 26:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Griffith, J P]]		[[Category: Griffith, J P]]
	[[Category: Serine/threonine protein kinase]]		[[Category: Serine/threonine protein kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 17:17, 11 August 2016

2016-08-11T17:17:09Z

← Older revision		Revision as of 17:17, 11 August 2016
Line 1:		Line 1:

	==Structure of PI3K gamma in complex with 1-[6-(5-methoxypyridin-3-yl)-1,3-benzothiazol-2-yl]-3-[2-(1-propyl-1H-imidazol-4-yl)ethyl]urea==		==Structure of PI3K gamma in complex with 1-[6-(5-methoxypyridin-3-yl)-1,3-benzothiazol-2-yl]-3-[2-(1-propyl-1H-imidazol-4-yl)ethyl]urea==
	<StructureSection load='4ps3' size='340' side='right' caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='4ps3' size='340' side='right' caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps3 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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [http://pdbe.org/4ps3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4ps3" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:42, 25 December 2014

2014-12-25T20:42:08Z

← Older revision		Revision as of 20:42, 25 December 2014
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	<StructureSection load='4ps3' size='340' side='right' caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='4ps3' size='340' side='right' caption='[[4ps3]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ps3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS3 OCA]. <br>		<table><tr><td colspan='2'>[[4ps3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PS3 FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2WH:1-[6-(5-METHOXYPYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2-YL]-3-[2-(1-PROPYL-1H-IMIDAZOL-4-YL)ETHYL]UREA'>2WH</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ps7\|4ps7]], [[4ps8\|4ps8]]</td></tr>
	<tr~~><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class~~='~~plainlinks~~'~~>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps3 PDBsum]</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=4ps3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ps3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps3 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	Structural Basis for Isoform Selectivity in a Class of Benzothiazole Inhibitors of Phosphoinositide 3-Kinase gamma,Collier PN, Martinez-Botella G, Cornebise M, Cottrell KM, Doran JD, Griffith JP, Mahajan S, Maltais F, Moody CS, Huck EP, Wang T, Aronov AM J Med Chem. 2014 May 2. PMID:24754609<ref>PMID:24754609</ref>		Structural Basis for Isoform Selectivity in a Class of Benzothiazole Inhibitors of Phosphoinositide 3-Kinase gamma,Collier PN, Martinez-Botella G, Cornebise M, Cottrell KM, Doran JD, Griffith JP, Mahajan S, Maltais F, Moody CS, Huck EP, Wang T, Aronov AM J Med Chem. 2014 May 2. PMID:24754609<ref>PMID:24754609</ref>

	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Griffith, J P.]]		[[Category: Griffith, J P]]
	[[Category: Serine/threonine protein kinase]]		[[Category: Serine/threonine protein kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:18, 14 May 2014

2014-05-14T07:18:12Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Structure of PI3K gamma in complex with 1-[6-(5-methoxypyridin-3-yl)-1,3-benzothiazol-2-yl]-3-[2-(1-propyl-1H-imidazol-4-yl)ethyl]urea==
-The entry 4ps3 is ON HOLD
+Structural Basis for Isoform Selectivity in a Class of Benzothiazole Inhibitors of Phosphoinositide 3-Kinase gamma,Collier PN, Martinez-Botella G, Cornebise M, Cottrell KM, Doran JD, Griffith JP, Mahajan S, Maltais F, Moody CS, Huck EP, Wang T, Aronov AM J Med Chem. 2014 May 2. PMID:24754609<ref>PMID:24754609</ref>
-Authors: Griffith, J.P.
+From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+== References ==

OCA at 07:40, 19 March 2014

2014-03-19T07:40:14Z

← Older revision		Revision as of 07:40, 19 March 2014
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	The entry 4ps3 is ON HOLD		The entry 4ps3 is ON HOLD

	Authors: Griffith, J.P		Authors: Griffith, J.P.

	Description: ~~Structural Basis for Isoform Selectivity of PI3K gamma~~		Description:

OCA: Protected "4ps3" [edit=sysop:move=sysop]

2014-03-12T12:38:09Z

Protected "4ps3" [edit=sysop:move=sysop]

← Older revision	Revision as of 12:38, 12 March 2014
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4ps3 is ON HOLD Authors: Griffith, J.P Description: Structural Basis for Isoform Selectivity of PI3K gamma

2014-03-12T12:38:07Z

New page: '''Unreleased structure''' The entry 4ps3 is ON HOLD Authors: Griffith, J.P Description: Structural Basis for Isoform Selectivity of PI3K gamma

New page

'''Unreleased structure'''

The entry 4ps3 is ON HOLD

Authors: Griffith, J.P

Description: Structural Basis for Isoform Selectivity of PI3K gamma