3oaw - Revision history

OCA at 10:33, 21 February 2024

OCA — Wed, 21 Feb 2024 10:33:43 GMT

←Older revision		Revision as of 10:33, 21 February 2024
Line 1:		Line 1:

	==4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors==		==4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors==
-	<StructureSection load='3oaw' size='340' side='right' caption='[[3oaw]], [[Resolution\|resolution]] 2.75Å' scene=''>	+	<StructureSection load='3oaw' size='340' side='right'caption='[[3oaw]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3oaw]] 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=3OAW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OAW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3oaw]] 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=3OAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OAW FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=OAW:2-AMINO-4-METHYL-8-(1-METHYLETHYL)-6-(1H-PYRAZOL-4-YL)PTERIDIN-7(8H)-ONE'>OAW</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]] 2.75Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ml9\|3ml9]]~~, [[~~3ml8~~\|~~3ml8~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OAW:2-AMINO-4-METHYL-8-(1-METHYLETHYL)-6-(1H-PYRAZOL-4-YL)PTERIDIN-7(8H)-ONE'>OAW</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PIK3CG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [https://pdbe.org/3oaw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [https://www.ebi.ac.uk/pdbsum/3oaw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oaw ProSAT]</span></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Phosphatidylinositol~~-4,5-~~bisphosphate_3~~-~~kinase Phosphatidylinositol~~-4,5-~~bisphosphate 3~~-~~kinase], with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153]~~ </~~span~~></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [~~http~~://pdbe.org/3oaw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3oaw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3oaw ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>	+	[https://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3oaw ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3oaw ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kalpha and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well.
-
-	4-Methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.,Liu KK, Bagrodia S, Bailey S, Cheng H, Chen H, Gao L, Greasley S, Hoffman JE, Hu Q, Johnson TO, Knighton D, Liu Z, Marx MA, Nambu MD, Ninkovic S, Pascual B, Rafidi K, Rodgers CM, Smith GL, Sun S, Wang H, Yang A, Yuan J, Zou A Bioorg Med Chem Lett. 2010 Oct 15;20(20):6096-9. Epub 2010 Aug 14. PMID:20817449<ref>PMID:20817449</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3oaw" style="background-color:#fffaf0;"></div>

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

OCA at 09:53, 30 January 2019

OCA — Wed, 30 Jan 2019 09:53:03 GMT

←Older revision		Revision as of 09:53, 30 January 2019
Line 16:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oa/3oaw_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oa/3oaw_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 13:40, 4 August 2016

OCA — Thu, 04 Aug 2016 13:40:30 GMT

←Older revision		Revision as of 13:40, 4 August 2016
Line 1:		Line 1:
		+
	==4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors==		==4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors==
	<StructureSection load='3oaw' size='340' side='right' caption='[[3oaw]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='3oaw' size='340' side='right' caption='[[3oaw]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3oaw]] 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=3OAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OAW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3oaw]] 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=3OAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OAW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OAW:2-AMINO-4-METHYL-8-(1-METHYLETHYL)-6-(1H-PYRAZOL-4-YL)PTERIDIN-7(8H)-ONE'>OAW</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OAW:2-AMINO-4-METHYL-8-(1-METHYLETHYL)-6-(1H-PYRAZOL-4-YL)PTERIDIN-7(8H)-ONE'>OAW</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ml9\|3ml9]], [[3ml8\|3ml8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ml9\|3ml9]], [[3ml8\|3ml8]]</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=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [http://www.ebi.ac.uk/pdbsum/3oaw 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=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [http://pdbe.org/3oaw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [http://www.ebi.ac.uk/pdbsum/3oaw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3oaw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3oaw ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 30:
	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 3oaw" style="background-color:#fffaf0;"></div>

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

OCA at 15:09, 24 December 2014

OCA — Wed, 24 Dec 2014 15:09:17 GMT

←Older revision		Revision as of 15:09, 24 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=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [http://www.ebi.ac.uk/pdbsum/3oaw 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=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [http://www.ebi.ac.uk/pdbsum/3oaw PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 12:46, 9 December 2014

OCA — Tue, 09 Dec 2014 12:46:16 GMT

←Older revision		Revision as of 12:46, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3oaw.~~png~~\|~~left~~\|200px]]	+	==4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors==
		+	<StructureSection load='3oaw' size='340' side='right' caption='[[3oaw]], [[Resolution\|resolution]] 2.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3oaw]] 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=3OAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OAW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OAW:2-AMINO-4-METHYL-8-(1-METHYLETHYL)-6-(1H-PYRAZOL-4-YL)PTERIDIN-7(8H)-ONE'>OAW</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ml9\|3ml9]], [[3ml8\|3ml8]]</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=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [http://www.ebi.ac.uk/pdbsum/3oaw PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oa/3oaw_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kalpha and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well.

-	~~{{STRUCTURE_3oaw\| PDB=3oaw \| SCENE= }}~~	+	4-Methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.,Liu KK, Bagrodia S, Bailey S, Cheng H, Chen H, Gao L, Greasley S, Hoffman JE, Hu Q, Johnson TO, Knighton D, Liu Z, Marx MA, Nambu MD, Ninkovic S, Pascual B, Rafidi K, Rodgers CM, Smith GL, Sun S, Wang H, Yang A, Yuan J, Zou A Bioorg Med Chem Lett. 2010 Oct 15;20(20):6096-9. Epub 2010 Aug 14. PMID:20817449<ref>PMID:20817449</ref>

-	~~===4-Methylpteridineones as Orally Active and Selective PI3K~~/~~mTOR Dual Inhibitors===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20817449}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3oaw]] 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=3OAW OCA].~~	+

	==See Also==		==See Also==
	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]		*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020817449<~~/~~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: Rodgers, C M.L.]]	+	[[Category: Rodgers, C M.L]]
	[[Category: Inhibition]]		[[Category: Inhibition]]
-	[[Category: Inhibitor complex.]]	+	[[Category: Inhibitor complex]]
	[[Category: Phosphoinositide kinase]]		[[Category: Phosphoinositide kinase]]
	[[Category: Transferase-transferase]]		[[Category: Transferase-transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:40, 20 October 2012

OCA — Sat, 20 Oct 2012 06:40:09 GMT

←Older revision		Revision as of 06:40, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3oaw]] 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=3OAW OCA].	+	[[3oaw]] 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=3OAW OCA].

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

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

OCA — Wed, 25 Jul 2012 13:56:08 GMT

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

←Older revision

Revision as of 13:56, 25 July 2012

OCA at 13:56, 25 July 2012

OCA — Wed, 25 Jul 2012 13:56:06 GMT

←Older revision		Revision as of 13:56, 25 July 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:3oaw.png\|left\|200px]]		[[Image:3oaw.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3oaw", 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_3oaw\| PDB=3oaw \| SCENE= }}		{{STRUCTURE_3oaw\| PDB=3oaw \| SCENE= }}

	===4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors===		===4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20817449}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20817449 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20817449}}		{{ABSTRACT_PUBMED_20817449}}

	==About this Structure==		==About this Structure==
-	~~3OAW~~ 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=3OAW OCA].	+	[[3oaw]] 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=3OAW OCA].
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20817449~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020817449</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 34:		Line 25:
	[[Category: Transferase-transferase]]		[[Category: Transferase-transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 6 05:33:47 2010''

OCA at 02:24, 6 October 2010

OCA — Wed, 06 Oct 2010 02:24:16 GMT

←Older revision		Revision as of 02:24, 6 October 2010
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:3oaw.~~jpg~~\|left\|200px]]	+	[[Image:3oaw.png\|left\|200px]]

	<!--		<!--
Line 35:		Line 35:
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Sep 22 14~~:49:15 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 6 05:33:47 2010''

OCA at 11:40, 22 September 2010

OCA — Wed, 22 Sep 2010 11:40:17 GMT

←Older revision		Revision as of 11:40, 22 September 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3oaw.jpg\|left\|200px]]

-	The ~~entry 3oaw~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3oaw", 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_3oaw\| PDB=3oaw \| SCENE= }}

-	~~Authors: Knighton, D.R., Greasley, S.E., Rodgers, C.M.~~-L.	+	===4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors===

-	Description: 4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Aug 18 11~~:25:59 2010''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20817449}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20817449 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20817449}}
		+
		+	==About this Structure==
		+	3OAW 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=3OAW OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20817449</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
		+	[[Category: Greasley, S E.]]
		+	[[Category: Knighton, D R.]]
		+	[[Category: Rodgers, C M.L.]]
		+	[[Category: Inhibition]]
		+	[[Category: Inhibitor complex.]]
		+	[[Category: Phosphoinositide kinase]]
		+	[[Category: Transferase-transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 22 14:49:15 2010''