6mum - Revision history

OCA at 06:39, 11 October 2023

OCA — Wed, 11 Oct 2023 06:39:14 GMT

←Older revision		Revision as of 06:39, 11 October 2023
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	<StructureSection load='6mum' size='340' side='right'caption='[[6mum]], [[Resolution\|resolution]] 3.06Å' scene=''>		<StructureSection load='6mum' size='340' side='right'caption='[[6mum]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mum]] is a 2 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=6MUM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MUM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mum]] is a 2 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=6MUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MUM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K47:[(3S)-3-{[8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-yl]oxy}pyrrolidin-1-yl](oxan-4-yl)methanone'>K47</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]] 3.06Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K47:[(3S)-3-{[8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-yl]oxy}pyrrolidin-1-yl](oxan-4-yl)methanone'>K47</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'>[https://proteopedia.org/fgij/fg.htm?mol=6mum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mum OCA], [https://pdbe.org/6mum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mum RCSB], [https://www.ebi.ac.uk/pdbsum/6mum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mum 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=6mum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mum OCA], [~~http~~://pdbe.org/6mum PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mum RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mum PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mum ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[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 ==
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	</div>		</div>
	<div class="pdbe-citations 6mum" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6mum" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice]]~~	+	[[Category: Mus musculus]]
-	~~[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase~~]]	+	[[Category: Fischmann TO]]
-	[[Category: Fischmann~~, T O]]~~	+
-	~~[[Category: Inflammatory disorder]]~~	+
-	~~[[Category: Isoform-specific inhibitor]]~~	+
-	~~[[Category: Phosphoinositide 3-kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:38, 23 May 2019

OCA — Thu, 23 May 2019 07:38:04 GMT

←Older revision		Revision as of 07:38, 23 May 2019
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	<StructureSection load='6mum' size='340' side='right'caption='[[6mum]], [[Resolution\|resolution]] 3.06Å' scene=''>		<StructureSection load='6mum' size='340' side='right'caption='[[6mum]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mum]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MUM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mum]] is a 2 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=6MUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MUM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K47:[(3S)-3-{[8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-yl]oxy}pyrrolidin-1-yl](oxan-4-yl)methanone'>K47</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K47:[(3S)-3-{[8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-yl]oxy}pyrrolidin-1-yl](oxan-4-yl)methanone'>K47</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=6mum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mum OCA], [http://pdbe.org/6mum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mum RCSB], [http://www.ebi.ac.uk/pdbsum/6mum PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mum 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=6mum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mum OCA], [http://pdbe.org/6mum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mum RCSB], [http://www.ebi.ac.uk/pdbsum/6mum PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mum ProSAT]</span></td></tr>
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	</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: Fischmann, T O]]		[[Category: Fischmann, T O]]

OCA at 08:53, 1 May 2019

OCA — Wed, 01 May 2019 08:53:21 GMT

←Older revision		Revision as of 08:53, 1 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6mum is ~~ON HOLD~~	+	==Murine PI3K delta kinsae domain - cpd 3==
		+	<StructureSection load='6mum' size='340' side='right'caption='[[6mum]], [[Resolution\|resolution]] 3.06Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6mum]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MUM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MUM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K47:[(3S)-3-{[8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-yl]oxy}pyrrolidin-1-yl](oxan-4-yl)methanone'>K47</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=6mum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mum OCA], [http://pdbe.org/6mum PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mum RCSB], [http://www.ebi.ac.uk/pdbsum/6mum PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mum ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	PI3Kdelta catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive. A purine PI3Kdelta inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury. Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif. Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile. A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.

-	~~Authors:~~ Fischmann, T.O.	+	Structure Overhaul Affords a Potent Purine PI3Kdelta Inhibitor with Improved Tolerability.,Methot JL, Zhou H, Kattar SD, McGowan MA, Wilson K, Garcia Y, Deng Y, Altman M, Fradera X, Lesburg C, Fischmann T, Li C, Alves S, Shah S, Fernandez R, Goldenblatt P, Hill A, Shaffer L, Chen D, Tong V, McLeod RL, Yu H, Bass A, Kemper R, Gatto NT, LaFranco-Scheuch L, Trotter BW, Guzi T, Katz JD J Med Chem. 2019 Apr 22. doi: 10.1021/acs.jmedchem.8b01818. PMID:30986068<ref>PMID:30986068</ref>

-	~~Description: Murine PI3K delta kinsae domain~~ -~~cpd 3~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Fischmann, T.O]]	+	<div class="pdbe-citations 6mum" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
		+	[[Category: Fischmann, T O]]
		+	[[Category: Inflammatory disorder]]
		+	[[Category: Isoform-specific inhibitor]]
		+	[[Category: Phosphoinositide 3-kinase]]
		+	[[Category: Transferase]]

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

OCA — Wed, 31 Oct 2018 05:34:28 GMT

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

←Older revision

Revision as of 05:34, 31 October 2018

OCA: New page: '''Unreleased structure''' The entry 6mum is ON HOLD Authors: Fischmann, T.O. Description: Murine PI3K delta kinsae domain -cpd 3 Category: Unreleased Structures [[Category: Fischm...

OCA — Wed, 31 Oct 2018 05:34:27 GMT

New page: '''Unreleased structure''' The entry 6mum is ON HOLD Authors: Fischmann, T.O. Description: Murine PI3K delta kinsae domain -cpd 3 Category: Unreleased Structures [[Category: Fischm...

New page

'''Unreleased structure'''

The entry 6mum is ON HOLD

Authors: Fischmann, T.O.

Description: Murine PI3K delta kinsae domain -cpd 3
[[Category: Unreleased Structures]]
[[Category: Fischmann, T.O]]