3p2b - Revision history

OCA at 10:38, 21 February 2024

2024-02-21T10:38:04Z

←Older revision		Revision as of 10:38, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3p2b' size='340' side='right'caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='3p2b' size='340' side='right'caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2B FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=P2B:3~~-[2~~-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</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]] 3.2Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PIK3CG, PK3CG ([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=P2B:3-[2-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Phosphatidylinositol~~-4,5-~~bisphosphate_3~~-~~kinase Phosphatidylinositol~~-~~4,5~~-~~bisphosphate~~ 3-~~kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [https://pdbe.org/3p2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [https://www.ebi.ac.uk/pdbsum/3p2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2b 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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [https://pdbe.org/3p2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [https://www.ebi.ac.uk/pdbsum/3p2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2b 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 ==~~	+
-	PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration, and differentiation. The PI3 kinase pathway is often de-regulated in cancer through PI3Kalpha overexpression, gene amplification, mutations, and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe a novel series of PI3K inhibitors sharing a pyrimidine core and showing significant potency against class I PI3 kinases in the biochemical assay and in cells. The discovery, synthesis and SAR of this chemotype are described.	+
-		+
-	Identification and structure-activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors.,Pecchi S, Renhowe PA, Taylor C, Kaufman S, Merritt H, Wiesmann M, Shoemaker KR, Knapp MS, Ornelas E, Hendrickson TF, Fantl W, Voliva CF Bioorg Med Chem Lett. 2010 Dec 1;20(23):6895-8. Epub 2010 Oct 13. PMID:21035331<ref>PMID:21035331</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3p2b" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]~~	+	[[Category: Elling RA]]
-	[[Category: Elling~~, R A~~]]	+	[[Category: Knapp MS]]
-	[[Category: Knapp~~, M S~~]]	+	[[Category: Ornelas E]]
-	[[Category: Ornelas, E]]	+
-	~~[[Category: Atp binding]]~~	+
-	~~[[Category: Lipid kinase]]~~	+
-	~~[[Category: Pi3-kinase p110 subunit gamma]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 11:11, 18 May 2022

2022-05-18T11:11:38Z

←Older revision		Revision as of 11:11, 18 May 2022
Line 1:		Line 1:

	==Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol==		==Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol==
-	<StructureSection load='3p2b' size='340' side='right' caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>	+	<StructureSection load='3p2b' size='340' side='right'caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3P2B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2B FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P2B:3-[2-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P2B:3-[2-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG, PK3CG ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG, PK3CG ([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'>[~~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'>[https://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [https://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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [~~http~~://pdbe.org/3p2b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3p2b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2b 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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [https://pdbe.org/3p2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [https://www.ebi.ac.uk/pdbsum/3p2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2b 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 ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[Phosphoinositide 3-~~Kinases~~\|Phosphoinositide 3-~~Kinases~~]]	+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Elling, R A]]		[[Category: Elling, R A]]

OCA at 01:37, 5 August 2016

2016-08-05T01:37:43Z

←Older revision		Revision as of 01:37, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol==		==Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol==
	<StructureSection load='3p2b' size='340' side='right' caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='3p2b' size='340' side='right' caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P2B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P2B FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P2B:3-[2-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P2B:3-[2-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG, PK3CG ([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, PK3CG ([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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [http://www.ebi.ac.uk/pdbsum/3p2b 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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [http://pdbe.org/3p2b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [http://www.ebi.ac.uk/pdbsum/3p2b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2b ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3p2b" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Elling, R A]]		[[Category: Elling, R A]]

OCA at 14:45, 25 December 2014

2014-12-25T14:45:54Z

←Older revision		Revision as of 14:45, 25 December 2014
Line 8:		Line 8:
	<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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [http://www.ebi.ac.uk/pdbsum/3p2b 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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [http://www.ebi.ac.uk/pdbsum/3p2b 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 ==

OCA at 12:49, 9 December 2014

2014-12-09T12:49:45Z

←Older revision		Revision as of 12:49, 9 December 2014
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-	[[~~Image:~~3p2b.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol==
		+	<StructureSection load='3p2b' size='340' side='right' caption='[[3p2b]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3p2b]] 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=3P2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P2B FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P2B:3-[2-MORPHOLIN-4-YL-6-(PYRIDIN-3-YLAMINO)PYRIMIDIN-4-YL]PHENOL'>P2B</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG, PK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3p2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2b RCSB], [http://www.ebi.ac.uk/pdbsum/3p2b PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration, and differentiation. The PI3 kinase pathway is often de-regulated in cancer through PI3Kalpha overexpression, gene amplification, mutations, and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe a novel series of PI3K inhibitors sharing a pyrimidine core and showing significant potency against class I PI3 kinases in the biochemical assay and in cells. The discovery, synthesis and SAR of this chemotype are described.

-	~~{{STRUCTURE_3p2b\| PDB=3p2b \| SCENE= }}~~	+	Identification and structure-activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors.,Pecchi S, Renhowe PA, Taylor C, Kaufman S, Merritt H, Wiesmann M, Shoemaker KR, Knapp MS, Ornelas E, Hendrickson TF, Fantl W, Voliva CF Bioorg Med Chem Lett. 2010 Dec 1;20(23):6895-8. Epub 2010 Oct 13. PMID:21035331<ref>PMID:21035331</ref>

-	~~===Crystal Structure~~ of ~~PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21035331}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3p2b]] 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=3P2B OCA].~~	+

	==See Also==		==See Also==
	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]		*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021035331<~~/~~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]]
-	[[Category: Elling, R A.]]	+	[[Category: Elling, R A]]
-	[[Category: Knapp, M S.]]	+	[[Category: Knapp, M S]]
-	[[Category: Ornelas, E.]]	+	[[Category: Ornelas, E]]
	[[Category: Atp binding]]		[[Category: Atp binding]]
	[[Category: Lipid kinase]]		[[Category: Lipid kinase]]

OCA at 17:58, 20 October 2012

2012-10-20T17:58:30Z

←Older revision		Revision as of 17:58, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[3p2b]] 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=3P2B OCA].	+	[[3p2b]] 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=3P2B OCA].

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

OCA at 02:35, 27 July 2012

2012-07-27T02:35:54Z

←Older revision		Revision as of 02:35, 27 July 2012
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-	[[Image:3p2b.~~jpg~~\|left\|200px]]	+	[[Image:3p2b.png\|left\|200px]]

-	<!--
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-	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_3p2b\| PDB=3p2b \| SCENE= }}		{{STRUCTURE_3p2b\| PDB=3p2b \| SCENE= }}

	===Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol===		===Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21035331}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21035331 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_21035331}}		{{ABSTRACT_PUBMED_21035331}}

	==About this Structure==		==About this Structure==
-	[[3p2b]] 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=3P2B OCA].	+	[[3p2b]] 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=3P2B OCA].
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]

	==Reference==		==Reference==

OCA: Protected "3p2b" [edit=sysop:move=sysop]

2011-08-17T06:16:30Z

Protected "3p2b" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:16, 17 August 2011

OCA at 06:16, 17 August 2011

2011-08-17T06:16:23Z

←Older revision		Revision as of 06:16, 17 August 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3p2b.jpg\|left\|200px]]

-	The ~~entry 3p2b~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3p2b", 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_3p2b\| PDB=3p2b \| SCENE= }}

-	~~Authors: Knapp, M.S., Elling, R.A., Ornelas, E.~~	+	===Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol===

-	Description: Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol

-	~~''Page seeded by~~ [http://oca.weizmann.ac.il/oca OCA ] ~~on Wed Dec 15 08~~:22:~~47 2010''~~	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21035331}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21035331 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21035331}}
		+
		+	==About this Structure==
		+	[[3p2b]] 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=3P2B OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021035331</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
		+	[[Category: Elling, R A.]]
		+	[[Category: Knapp, M S.]]
		+	[[Category: Ornelas, E.]]
		+	[[Category: Atp binding]]
		+	[[Category: Lipid kinase]]
		+	[[Category: Pi3-kinase p110 subunit gamma]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:10, 15 December 2010

2010-12-15T05:10:27Z

←Older revision		Revision as of 05:10, 15 December 2010
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3p2b is ON HOLD	+	The entry 3p2b is ON HOLD until Paper Publication

	Authors: Knapp, M.S., Elling, R.A., Ornelas, E.		Authors: Knapp, M.S., Elling, R.A., Ornelas, E.
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	Description: Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol		Description: Crystal Structure of PI3K gamma with 3-(2-morpholino-6-(pyridin-3-ylamino)pyrimidin-4-yl)phenol

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Oct 13 10~~:33:07 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 15 08:22:47 2010''