7lq1 - Revision history

OCA at 07:18, 3 April 2024

2024-04-03T07:18:30Z

←Older revision		Revision as of 07:18, 3 April 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7lq1]] is a 2 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=7LQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQ1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7lq1]] is a 2 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=7LQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQ1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=YA7:N-(5-(6-(2-((2S,6R)-2,6-dimethylmorpholino)pyridin-4-yl)-1-oxoisoindolin-4-yl)-2-methoxypyridin-3-yl)methanesulfonamide'>YA7</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]] 2.96Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=YA7:N-(5-(6-(2-((2S,6R)-2,6-dimethylmorpholino)pyridin-4-yl)-1-oxoisoindolin-4-yl)-2-methoxypyridin-3-yl)methanesulfonamide'>YA7</scene></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=7lq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lq1 OCA], [https://pdbe.org/7lq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7lq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lq1 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=7lq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lq1 OCA], [https://pdbe.org/7lq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7lq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lq1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/PK3CD_HUMAN PK3CD_HUMAN]] Activated PIK3-delta syndrome. The disease is caused by mutations affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/PK3CD_HUMAN PK3CD_HUMAN] Activated PIK3-delta syndrome. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PK3CD_HUMAN PK3CD_HUMAN]] 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. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.<ref>PMID:20081091</ref> <ref>PMID:22020336</ref>	+	[https://www.uniprot.org/uniprot/PK3CD_HUMAN PK3CD_HUMAN] 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. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.<ref>PMID:20081091</ref> <ref>PMID:22020336</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	PI3K-delta mediates key immune cell signaling pathways and is a target of interest for treatment of oncological and immunological disorders. Here we describe the discovery and optimization of a novel series of PI3K-delta selective inhibitors. We first identified hits containing an isoindolinone scaffold using a combined ligand- and receptor-based virtual screening workflow, and then improved potency and selectivity guided by structural data and modeling. Careful optimization of molecular properties led to compounds with improved permeability and pharmacokinetic profile, and high potency in a whole blood assay.	+
-		+
-	Discovery of a new series of PI3K-delta inhibitors from Virtual Screening.,Fradera X, Deng Q, Achab A, Garcia Y, Kattar SD, McGowan MA, Methot JL, Wilson K, Zhou H, Shaffer L, Goldenblatt P, Tong V, Augustin MA, Altman MD, Lesburg CA, Shah S, Katz JD Bioorg Med Chem Lett. 2021 Jun 15;42:128046. doi: 10.1016/j.bmcl.2021.128046., Epub 2021 Apr 16. PMID:33865969<ref>PMID:33865969</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 7lq1" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:44, 7 September 2022

2022-09-07T19:44:32Z

←Older revision		Revision as of 19:44, 7 September 2022
Line 1:		Line 1:

-	====	+	==HUMAN PI3KDELTA IN COMPLEX WITH COMPOUND 28==
-	<StructureSection load='7lq1' size='340' side='right'caption='[[7lq1]]' scene=''>	+	<StructureSection load='7lq1' size='340' side='right'caption='[[7lq1]], [[Resolution\|resolution]] 2.96Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lq1]] is a 2 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=7LQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQ1 FirstGlance]. <br>
-	</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=7lq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lq1 OCA], [https://pdbe.org/7lq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7lq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lq1 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=YA7:N-(5-(6-(2-((2S,6R)-2,6-dimethylmorpholino)pyridin-4-yl)-1-oxoisoindolin-4-yl)-2-methoxypyridin-3-yl)methanesulfonamide'>YA7</scene></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=7lq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lq1 OCA], [https://pdbe.org/7lq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7lq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lq1 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/PK3CD_HUMAN PK3CD_HUMAN]] Activated PIK3-delta syndrome. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/PK3CD_HUMAN PK3CD_HUMAN]] 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. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.<ref>PMID:20081091</ref> <ref>PMID:22020336</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	PI3K-delta mediates key immune cell signaling pathways and is a target of interest for treatment of oncological and immunological disorders. Here we describe the discovery and optimization of a novel series of PI3K-delta selective inhibitors. We first identified hits containing an isoindolinone scaffold using a combined ligand- and receptor-based virtual screening workflow, and then improved potency and selectivity guided by structural data and modeling. Careful optimization of molecular properties led to compounds with improved permeability and pharmacokinetic profile, and high potency in a whole blood assay.
		+
		+	Discovery of a new series of PI3K-delta inhibitors from Virtual Screening.,Fradera X, Deng Q, Achab A, Garcia Y, Kattar SD, McGowan MA, Methot JL, Wilson K, Zhou H, Shaffer L, Goldenblatt P, Tong V, Augustin MA, Altman MD, Lesburg CA, Shah S, Katz JD Bioorg Med Chem Lett. 2021 Jun 15;42:128046. doi: 10.1016/j.bmcl.2021.128046., Epub 2021 Apr 16. PMID:33865969<ref>PMID:33865969</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lq1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Augustin M]]
		+	[[Category: Lesburg CA]]

OCA at 10:15, 16 February 2022

2022-02-16T10:15:58Z

←Older revision		Revision as of 10:15, 16 February 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7lq1 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7lq1' size='340' side='right'caption='[[7lq1]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7lq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lq1 OCA], [https://pdbe.org/7lq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7lq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lq1 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA: Protected "7lq1" [edit=sysop:move=sysop]

2021-02-24T05:39:54Z

Protected "7lq1" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:39, 24 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lq1 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2021-02-24T05:39:53Z

New page: '''Unreleased structure''' The entry 7lq1 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7lq1 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]