6ftn - Revision history

OCA at 07:33, 1 May 2024

OCA — Wed, 01 May 2024 07:33:21 GMT

←Older revision		Revision as of 07:33, 1 May 2024
Line 1:		Line 1:

	==mPI3Kd IN COMPLEX WITH AZ2==		==mPI3Kd IN COMPLEX WITH AZ2==
-	<StructureSection load='6ftn' size='340' side='right' caption='[[6ftn]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='6ftn' size='340' side='right'caption='[[6ftn]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ftn]] 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=6FTN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6FTN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ftn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FTN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E78:~{N}-[5-[2-[(1~{S})-1-cyclopropylethyl]-7-methyl-1-oxidanylidene-3~{H}-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]ethanamide'>E78</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]] 2Å</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=6ftn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftn OCA], [~~http~~://pdbe.org/6ftn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ftn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ftn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftn ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E78:~{N}-[5-[2-[(1~{S})-1-cyclopropylethyl]-7-methyl-1-oxidanylidene-3~{H}-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]ethanamide'>E78</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=6ftn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftn OCA], [https://pdbe.org/6ftn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ftn RCSB], [https://www.ebi.ac.uk/pdbsum/6ftn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftn 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kgamma inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kgamma inhibitor with ADME properties suitable for oral administration. Compound 15 was advanced into in vivo studies showing dose-dependent inhibition of LPS-induced airway neutrophilia in rats when administered orally.	+

-	~~Discovery of Highly Isoform Selective Orally Bioavailable~~ Phosphoinositide 3-Kinase (PI3K)-gamma Inhibitors.,Pemberton N, Mogemark M, Arlbrandt S, Bold P, Cox RJ, Gardelli C, Holden NS, Karabelas K, Karlsson J, Lever S, Li X, Lindmark H, Norberg M, Perry MWD, Petersen J, Rodrigo Blomqvist S, Thomas M, Tyrchan C, Westin Eriksson A, Zlatoidsky P, Oster L J Med Chem. 2018 Jun 18. doi: 10.1021/acs.jmedchem.8b00447. PMID:29852070<ref>PMID:29852070</ref>	+	==See Also==
-		+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6ftn" style="background~~-~~color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Petersen, J~~]]	+	[[Category: Mus musculus]]
-	[[Category: ~~Mi3kd]]~~	+	[[Category: Petersen J]]
-	~~[[Category: Transferase~~]]	+

OCA at 06:18, 11 July 2018

OCA — Wed, 11 Jul 2018 06:18:05 GMT

←Older revision		Revision as of 06:18, 11 July 2018
Line 3:		Line 3:
	<StructureSection load='6ftn' size='340' side='right' caption='[[6ftn]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6ftn' size='340' side='right' caption='[[6ftn]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ftn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FTN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ftn]] 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=6FTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FTN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E78:~{N}-[5-[2-[(1~{S})-1-cyclopropylethyl]-7-methyl-1-oxidanylidene-3~{H}-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]ethanamide'>E78</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E78:~{N}-[5-[2-[(1~{S})-1-cyclopropylethyl]-7-methyl-1-oxidanylidene-3~{H}-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]ethanamide'>E78</scene></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=6ftn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftn OCA], [http://pdbe.org/6ftn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ftn RCSB], [http://www.ebi.ac.uk/pdbsum/6ftn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftn 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=6ftn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftn OCA], [http://pdbe.org/6ftn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ftn RCSB], [http://www.ebi.ac.uk/pdbsum/6ftn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftn ProSAT]</span></td></tr>
Line 22:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Petersen, J]]		[[Category: Petersen, J]]
	[[Category: Mi3kd]]		[[Category: Mi3kd]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 05:55, 20 June 2018

OCA — Wed, 20 Jun 2018 05:55:17 GMT

←Older revision		Revision as of 05:55, 20 June 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ftn is ~~ON HOLD~~	+	==mPI3Kd IN COMPLEX WITH AZ2==
		+	<StructureSection load='6ftn' size='340' side='right' caption='[[6ftn]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ftn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FTN FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E78:~{N}-[5-[2-[(1~{S})-1-cyclopropylethyl]-7-methyl-1-oxidanylidene-3~{H}-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]ethanamide'>E78</scene></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=6ftn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftn OCA], [http://pdbe.org/6ftn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ftn RCSB], [http://www.ebi.ac.uk/pdbsum/6ftn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftn 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 ==
		+	In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kgamma inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kgamma inhibitor with ADME properties suitable for oral administration. Compound 15 was advanced into in vivo studies showing dose-dependent inhibition of LPS-induced airway neutrophilia in rats when administered orally.

-	~~Authors:~~ Petersen, J.	+	Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-gamma Inhibitors.,Pemberton N, Mogemark M, Arlbrandt S, Bold P, Cox RJ, Gardelli C, Holden NS, Karabelas K, Karlsson J, Lever S, Li X, Lindmark H, Norberg M, Perry MWD, Petersen J, Rodrigo Blomqvist S, Thomas M, Tyrchan C, Westin Eriksson A, Zlatoidsky P, Oster L J Med Chem. 2018 Jun 18. doi: 10.1021/acs.jmedchem.8b00447. PMID:29852070<ref>PMID:29852070</ref>

-	~~Description: mPI3Kd IN COMPLEX WITH AZ2~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 6ftn" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Petersen, J]]		[[Category: Petersen, J]]
		+	[[Category: Mi3kd]]
		+	[[Category: Transferase]]

OCA at 05:49, 14 June 2018

OCA — Thu, 14 Jun 2018 05:49:05 GMT

←Older revision		Revision as of 05:49, 14 June 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ftn is ON HOLD ~~until sometime in the future~~	+	The entry 6ftn is ON HOLD

	Authors: Petersen, J.		Authors: Petersen, J.

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

OCA — Wed, 28 Feb 2018 05:15:14 GMT

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

←Older revision

Revision as of 05:15, 28 February 2018

OCA: New page: '''Unreleased structure''' The entry 6ftn is ON HOLD until sometime in the future Authors: Petersen, J. Description: mPI3Kd IN COMPLEX WITH AZ2 Category: Unreleased Structures [[Ca...

OCA — Wed, 28 Feb 2018 05:15:13 GMT

New page: '''Unreleased structure''' The entry 6ftn is ON HOLD until sometime in the future Authors: Petersen, J. Description: mPI3Kd IN COMPLEX WITH AZ2 Category: Unreleased Structures [[Ca...

New page

'''Unreleased structure'''

The entry 6ftn is ON HOLD until sometime in the future

Authors: Petersen, J.

Description: mPI3Kd IN COMPLEX WITH AZ2
[[Category: Unreleased Structures]]
[[Category: Petersen, J]]