3ps6 - Revision history

OCA at 10:43, 21 February 2024

2024-02-21T10:43:09Z

←Older revision		Revision as of 10:43, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3ps6' size='340' side='right'caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3ps6' size='340' side='right'caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=3PS:4~~-~~AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</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]] 2.6Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3oaw\|3oaw]], [[3ml8\|3ml8]], [[3ml9\|3ml9]], [[3pre\|3pre]], [[3prz\|3prz]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PS:4-AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PIK3CG ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [https://pdbe.org/3ps6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ps6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ps6 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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [https://pdbe.org/3ps6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ps6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ps6 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 ==~~	+
-	Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3-D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kgamma enzyme. In addition, a novel synthetic route was developed for these analogs.	+
-		+
-	Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.,Liu KK, Huang X, Bagrodia S, Chen JH, Greasley S, Cheng H, Sun S, Knighton D, Rodgers C, Rafidi K, Zou A, Xiao J, Yan S Bioorg Med Chem Lett. 2011 Feb 15;21(4):1270-4. Epub 2010 Dec 10. PMID:21269826<ref>PMID:21269826</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3ps6" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]~~	+	[[Category: Greasley SE]]
-	[[Category: Greasley~~, S E~~]]	+	[[Category: Knighton DR]]
-	[[Category: Knighton~~, D R~~]]	+	[[Category: Rogers CM-L]]
-	[[Category: Rogers~~, C M.~~L]]	+
-	~~[[Category: Phosphoinositide kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:52, 25 May 2022

2022-05-25T08:52:37Z

←Older revision		Revision as of 08:52, 25 May 2022
Line 1:		Line 1:

	==Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.==		==Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.==
-	<StructureSection load='3ps6' size='340' side='right' caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='3ps6' size='340' side='right'caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PS:4-AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PS:4-AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3oaw\|3oaw]], [[3ml8\|3ml8]], [[3ml9\|3ml9]], [[3pre\|3pre]], [[3prz\|3prz]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3oaw\|3oaw]], [[3ml8\|3ml8]], [[3ml9\|3ml9]], [[3pre\|3pre]], [[3prz\|3prz]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CG ([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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [~~http~~://pdbe.org/3ps6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3ps6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3ps6 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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [https://pdbe.org/3ps6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ps6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ps6 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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	</div>		</div>
	<div class="pdbe-citations 3ps6" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ps6" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Greasley, S E]]		[[Category: Greasley, S E]]

OCA at 19:31, 24 January 2018

2018-01-24T19:31:57Z

←Older revision		Revision as of 19:31, 24 January 2018
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3ps6" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ps6" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:14, 5 August 2016

2016-08-05T05:14:46Z

←Older revision		Revision as of 05:14, 5 August 2016
Line 1:		Line 1:
		+
	==Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.==		==Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.==
	<StructureSection load='3ps6' size='340' side='right' caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3ps6' size='340' side='right' caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PS:4-AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PS:4-AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3oaw\|3oaw]], [[3ml8\|3ml8]], [[3ml9\|3ml9]], [[3pre\|3pre]], [[3prz\|3prz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3oaw\|3oaw]], [[3ml8\|3ml8]], [[3ml9\|3ml9]], [[3pre\|3pre]], [[3prz\|3prz]]</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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ps6 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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [http://pdbe.org/3ps6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ps6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ps6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3ps6" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Greasley, S E]]		[[Category: Greasley, S E]]

OCA at 16:02, 25 December 2014

2014-12-25T16:02:47Z

←Older revision		Revision as of 16:02, 25 December 2014
Line 9:		Line 9:
	<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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ps6 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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ps6 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 10:33, 9 December 2014

2014-12-09T10:33:24Z

←Older revision		Revision as of 10:33, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3ps6.~~png~~\|~~left~~\|~~200px~~]]	+	==Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.==
		+	<StructureSection load='3ps6' size='340' side='right' caption='[[3ps6]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3ps6]] 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=3PS6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PS6 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PS:4-AMINO-N-(6-METHOXYPYRIDIN-3-YL)-2-METHYLQUINAZOLINE-8-CARBOXAMIDE'>3PS</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3oaw\|3oaw]], [[3ml8\|3ml8]], [[3ml9\|3ml9]], [[3pre\|3pre]], [[3prz\|3prz]]</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='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=3ps6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ps6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ps6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ps6 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3-D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kgamma enzyme. In addition, a novel synthetic route was developed for these analogs.

-	~~{{STRUCTURE_3ps6\| PDB=3ps6 \| SCENE= }}~~	+	Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.,Liu KK, Huang X, Bagrodia S, Chen JH, Greasley S, Cheng H, Sun S, Knighton D, Rodgers C, Rafidi K, Zou A, Xiao J, Yan S Bioorg Med Chem Lett. 2011 Feb 15;21(4):1270-4. Epub 2010 Dec 10. PMID:21269826<ref>PMID:21269826</ref>

-	~~===Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K~~/~~mTOR dual inhibitors.===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21269826}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3ps6]] 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=3PS6 OCA].~~	+

	==See Also==		==See Also==
	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]		*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021269826<~~/~~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: Greasley, S E.]]	+	[[Category: Greasley, S E]]
-	[[Category: Knighton, D R.]]	+	[[Category: Knighton, D R]]
	[[Category: Rogers, C M.L]]		[[Category: Rogers, C M.L]]
	[[Category: Phosphoinositide kinase]]		[[Category: Phosphoinositide kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 18:40, 20 October 2012

2012-10-20T18:40:30Z

←Older revision		Revision as of 18:40, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3ps6]] 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=3PS6 OCA].	+	[[3ps6]] 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=3PS6 OCA].

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

OCA at 04:50, 27 July 2012

2012-07-27T04:50:47Z

←Older revision		Revision as of 04:50, 27 July 2012
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	[[Image:3ps6.png\|left\|200px]]		[[Image:3ps6.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_3ps6\| PDB=3ps6 \| SCENE= }}		{{STRUCTURE_3ps6\| PDB=3ps6 \| SCENE= }}

	===Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.===		===Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.===

-
-	<!--
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	{{ABSTRACT_PUBMED_21269826}}		{{ABSTRACT_PUBMED_21269826}}

	==About this Structure==		==About this Structure==
-	[[3ps6]] 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=3PS6 OCA].	+	[[3ps6]] 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=3PS6 OCA].
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21269826~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021269826</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
Line 28:		Line 20:
	[[Category: Knighton, D R.]]		[[Category: Knighton, D R.]]
	[[Category: Rogers, C M.L]]		[[Category: Rogers, C M.L]]
		+	[[Category: Phosphoinositide kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:17, 23 February 2011

2011-02-23T09:17:56Z

←Older revision		Revision as of 09:17, 23 February 2011
Line 1:		Line 1:
-	[[Image:3ps6.~~jpg~~\|left\|200px]]	+	[[Image:3ps6.png\|left\|200px]]

	<!--		<!--

OCA: Protected "3ps6" [edit=sysop:move=sysop]

2011-02-09T06:13:00Z

Protected "3ps6" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:13, 9 February 2011