6tns - Revision history

OCA at 08:54, 29 September 2021

OCA — Wed, 29 Sep 2021 08:54:41 GMT

←Older revision		Revision as of 08:54, 29 September 2021
Line 3:		Line 3:
	<StructureSection load='6tns' size='340' side='right'caption='[[6tns]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='6tns' size='340' side='right'caption='[[6tns]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6tns]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6TNS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6tns]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TNS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NQ5:2-methoxy-~{N}-[2-methoxy-5-[7-[[(2~{R})-4-(oxetan-3-yl)morpholin-2-yl]methoxy]-1,3-dihydro-2-benzofuran-5-yl]pyridin-3-yl]ethanesulfonamide'>NQ5</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NQ5:2-methoxy-~{N}-[2-methoxy-5-[7-[[(2~{R})-4-(oxetan-3-yl)morpholin-2-yl]methoxy]-1,3-dihydro-2-benzofuran-5-yl]pyridin-3-yl]ethanesulfonamide'>NQ5</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Pik3cd ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Pik3cd ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6tns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tns OCA], [~~http~~://pdbe.org/6tns PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6tns RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6tns PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6tns 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=6tns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tns OCA], [https://pdbe.org/6tns PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tns RCSB], [https://www.ebi.ac.uk/pdbsum/6tns PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tns ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PK3CD_MOUSE PK3CD_MOUSE]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function.<ref>PMID:12130661</ref> <ref>PMID:12235209</ref> <ref>PMID:15496927</ref> <ref>PMID:16116162</ref> <ref>PMID:18259608</ref> <ref>PMID:18809712</ref> <ref>PMID:19297623</ref>	+	[[https://www.uniprot.org/uniprot/PK3CD_MOUSE PK3CD_MOUSE]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function.<ref>PMID:12130661</ref> <ref>PMID:12235209</ref> <ref>PMID:15496927</ref> <ref>PMID:16116162</ref> <ref>PMID:18259608</ref> <ref>PMID:18809712</ref> <ref>PMID:19297623</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 09:06, 5 February 2020

OCA — Wed, 05 Feb 2020 09:06:38 GMT

←Older revision		Revision as of 09:06, 5 February 2020
Line 3:		Line 3:
	<StructureSection load='6tns' size='340' side='right'caption='[[6tns]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='6tns' size='340' side='right'caption='[[6tns]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6tns]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TNS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6tns]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TNS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NQ5:2-methoxy-~{N}-[2-methoxy-5-[7-[[(2~{R})-4-(oxetan-3-yl)morpholin-2-yl]methoxy]-1,3-dihydro-2-benzofuran-5-yl]pyridin-3-yl]ethanesulfonamide'>NQ5</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NQ5:2-methoxy-~{N}-[2-methoxy-5-[7-[[(2~{R})-4-(oxetan-3-yl)morpholin-2-yl]methoxy]-1,3-dihydro-2-benzofuran-5-yl]pyridin-3-yl]ethanesulfonamide'>NQ5</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Pik3cd ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6tns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tns OCA], [http://pdbe.org/6tns PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tns RCSB], [http://www.ebi.ac.uk/pdbsum/6tns PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tns ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6tns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tns OCA], [http://pdbe.org/6tns PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tns RCSB], [http://www.ebi.ac.uk/pdbsum/6tns PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tns ProSAT]</span></td></tr>
Line 24:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]		[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Barton, N]]		[[Category: Barton, N]]

OCA at 08:26, 1 January 2020

OCA — Wed, 01 Jan 2020 08:26:25 GMT

←Older revision		Revision as of 08:26, 1 January 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6tns is ~~ON HOLD~~	+	==PI3K delta in complex with 2methoxyN[2methoxy5(7{[(2R)4(oxetan3 yl)morpholin2yl]methoxy}1,3dihydro2 benzofuran5yl)pyridin3yl]ethane1 sulfonamide==
		+	<StructureSection load='6tns' size='340' side='right'caption='[[6tns]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6tns]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TNS FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NQ5:2-methoxy-~{N}-[2-methoxy-5-[7-[[(2~{R})-4-(oxetan-3-yl)morpholin-2-yl]methoxy]-1,3-dihydro-2-benzofuran-5-yl]pyridin-3-yl]ethanesulfonamide'>NQ5</scene></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=6tns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tns OCA], [http://pdbe.org/6tns PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tns RCSB], [http://www.ebi.ac.uk/pdbsum/6tns PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tns ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PK3CD_MOUSE PK3CD_MOUSE]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function.<ref>PMID:12130661</ref> <ref>PMID:12235209</ref> <ref>PMID:15496927</ref> <ref>PMID:16116162</ref> <ref>PMID:18259608</ref> <ref>PMID:18809712</ref> <ref>PMID:19297623</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Optimisation of a lead series of PI3Kdelta inhibitors based on a dihydroisobenzofuran core led to the identification of potent, orally bioavailable compound 19. Selectivity profiling of compound 19 showed similar potency for the class III PI3K, Vps34, as for PI3Kdelta and compound 19 was not well-tolerated in a 7 day rat toxicity study. Structure-based design led to an improvement in selectivity for PI3Kdelta over Vps34 and a focus on oral PK properties resulted in the discovery of compound 41, which showed improved toxicological outcomes at similar exposures to compound 19.

-	~~Authors:~~ Convery, M~~.A.~~, ~~Rowland~~, P., ~~Henley~~, ~~Z.A.~~, ~~Barton~~, N.~~, Down, K~~.	+	Optimization of Orally Bioavailable PI3Kdelta Inhibitors and Identification of Vps34 as a key off-target activity.,Henley ZA, Amour A, Barton N, Bantscheff M, Bergamini G, Bertrand SM, Convery MA, Down KD, Duempelfeld B, Edwards CD, Grandi P, Gore PM, Keeling S, Livia S, Mallett DN, Maxwell AC, Price M, Rau C, Reinhard F, Rowedder JE, Rowland P, Taylor J, Thomas D, Hessel EM, Hamblin N J Med Chem. 2019 Dec 19. doi: 10.1021/acs.jmedchem.9b01585. PMID:31855425<ref>PMID:31855425</ref>

-	~~Description: PI3K delta in complex with 2methoxyN[2methoxy5(7{[(2R)4(oxetan3 yl)morpholin2yl]methoxy}1~~,~~3dihydro2 benzofuran5yl)pyridin3yl]ethane1 sulfonamide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Rowland~~, P]]	+	<div class="pdbe-citations 6tns" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
	[[Category: Barton, N]]		[[Category: Barton, N]]
-	~~[[Category: Henley, Z.A]]~~	+	[[Category: Convery, M A]]
-	[[Category: Convery, M.A]]	+
	[[Category: Down, K]]		[[Category: Down, K]]
		+	[[Category: Henley, Z A]]
		+	[[Category: Rowland, P]]
		+	[[Category: Pi3 kinase structure based design]]
		+	[[Category: Transferase]]

OCA: Protected "6tns" [edit=sysop:move=sysop]

OCA — Wed, 18 Dec 2019 05:52:58 GMT

Protected "6tns" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:52, 18 December 2019

OCA: New page: '''Unreleased structure''' The entry 6tns is ON HOLD Authors: Convery, M.A., Rowland, P., Henley, Z.A., Barton, N., Down, K. Description: PI3K delta in complex with 2methoxyN[2methoxy5...

OCA — Wed, 18 Dec 2019 05:52:56 GMT

New page: '''Unreleased structure''' The entry 6tns is ON HOLD Authors: Convery, M.A., Rowland, P., Henley, Z.A., Barton, N., Down, K. Description: PI3K delta in complex with 2methoxyN[2methoxy5...

New page

'''Unreleased structure'''

The entry 6tns is ON HOLD

Authors: Convery, M.A., Rowland, P., Henley, Z.A., Barton, N., Down, K.

Description: PI3K delta in complex with 2methoxyN[2methoxy5(7{[(2R)4(oxetan3 yl)morpholin2yl]methoxy}1,3dihydro2 benzofuran5yl)pyridin3yl]ethane1 sulfonamide
[[Category: Unreleased Structures]]
[[Category: Rowland, P]]
[[Category: Barton, N]]
[[Category: Henley, Z.A]]
[[Category: Convery, M.A]]
[[Category: Down, K]]