5kae - Revision history

OCA at 09:57, 27 September 2023

OCA — Wed, 27 Sep 2023 09:57:10 GMT

←Older revision		Revision as of 09:57, 27 September 2023
Line 1:		Line 1:

	==Crystal structure of human PI3K-gamma in complex with quinoline-containing inhibitor 5g==		==Crystal structure of human PI3K-gamma in complex with quinoline-containing inhibitor 5g==
-	<StructureSection load='5kae' size='340' side='right' caption='[[5kae]], [[Resolution\|resolution]] 2.65Å' scene=''>	+	<StructureSection load='5kae' size='340' side='right'caption='[[5kae]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kae]] 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=5KAE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5KAE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kae]] 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=5KAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KAE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6RF:4-azanyl-6-[[(1~{S})-1-(6-fluoranyl-3-phenyl-4-piperazin-1-ylcarbonyl-quinolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile'>6RF</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]] 2.65Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6RF:4-azanyl-6-[[(1~{S})-1-(6-fluoranyl-3-phenyl-4-piperazin-1-ylcarbonyl-quinolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile'>6RF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5kae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kae OCA], [~~http~~://pdbe.org/5kae PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5kae RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5kae PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5kae 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=5kae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kae OCA], [https://pdbe.org/5kae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kae RCSB], [https://www.ebi.ac.uk/pdbsum/5kae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kae 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>
		+
		+	==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: ~~Tang, J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Whittington, D A~~]]	+	[[Category: Tang J]]
-	[[Category: ~~Yakowec, P~~]]	+	[[Category: Whittington DA]]
-	[[Category: ~~Inflammatory disease]]~~	+	[[Category: Yakowec P]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Phosphotransferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:36, 16 November 2017

OCA — Thu, 16 Nov 2017 08:36:44 GMT

←Older revision		Revision as of 08:36, 16 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5kae is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human PI3K-gamma in complex with quinoline-containing inhibitor 5g==
-		+	<StructureSection load='5kae' size='340' side='right' caption='[[5kae]], [[Resolution\|resolution]] 2.65Å' scene=''>
-	~~Authors~~: ~~Whittington~~, D.A., ~~Tang~~, J., ~~Yakowec~~, P.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5kae]] 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=5KAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KAE FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of human~~ PI3K-~~gamma~~ in ~~complex~~ with ~~quinoline~~-~~containing inhibitor 5g~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6RF:4-azanyl-6-[[(1~{S})-1-(6-fluoranyl-3-phenyl-4-piperazin-1-ylcarbonyl-quinolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile'>6RF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kae OCA], [http://pdbe.org/5kae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kae RCSB], [http://www.ebi.ac.uk/pdbsum/5kae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kae ProSAT]</span></td></tr>
		+	</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Tang, J]]		[[Category: Tang, J]]
		+	[[Category: Whittington, D A]]
	[[Category: Yakowec, P]]		[[Category: Yakowec, P]]
-	[[Category: ~~Whittington, D.A~~]]	+	[[Category: Inflammatory disease]]
		+	[[Category: Inhibitor]]
		+	[[Category: Phosphotransferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:13, 9 March 2017

OCA — Thu, 09 Mar 2017 10:13:42 GMT

←Older revision		Revision as of 10:13, 9 March 2017
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Tang, J]]		[[Category: Tang, J]]
-	[[Category: Whittington, D.A]]
	[[Category: Yakowec, P]]		[[Category: Yakowec, P]]
		+	[[Category: Whittington, D.A]]

OCA at 09:07, 14 July 2016

OCA — Thu, 14 Jul 2016 09:07:09 GMT

←Older revision		Revision as of 09:07, 14 July 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5kae is ON HOLD	+	The entry 5kae is ON HOLD until Paper Publication

	Authors: Whittington, D.A., Tang, J., Yakowec, P.		Authors: Whittington, D.A., Tang, J., Yakowec, P.

OCA: Protected "5kae" [edit=sysop:move=sysop]

OCA — Mon, 20 Jun 2016 13:38:05 GMT

Protected "5kae" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:38, 20 June 2016

OCA: New page: '''Unreleased structure''' The entry 5kae is ON HOLD Authors: Whittington, D.A., Tang, J., Yakowec, P. Description: Crystal structure of human PI3K-gamma in complex with quinoline-cont...

OCA — Mon, 20 Jun 2016 13:38:04 GMT

New page: '''Unreleased structure''' The entry 5kae is ON HOLD Authors: Whittington, D.A., Tang, J., Yakowec, P. Description: Crystal structure of human PI3K-gamma in complex with quinoline-cont...

New page

'''Unreleased structure'''

The entry 5kae is ON HOLD

Authors: Whittington, D.A., Tang, J., Yakowec, P.

Description: Crystal structure of human PI3K-gamma in complex with quinoline-containing inhibitor 5g
[[Category: Unreleased Structures]]
[[Category: Tang, J]]
[[Category: Whittington, D.A]]
[[Category: Yakowec, P]]