OCA at 06:51, 12 December 2018

OCA — Wed, 12 Dec 2018 06:51:00 GMT

←Older revision		Revision as of 06:51, 12 December 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6hho is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of RIP1 kinase in complex with GSK547==
		+	<StructureSection load='6hho' size='340' side='right' caption='[[6hho]], [[Resolution\|resolution]] 3.49Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hho]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HHO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G4W:6-[4-[(5~{S})-5-[3,5-bis(fluoranyl)phenyl]pyrazolidin-1-yl]carbonylpiperidin-1-yl]pyrimidine-4-carbonitrile'>G4W</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=6hho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hho OCA], [http://pdbe.org/6hho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hho RCSB], [http://www.ebi.ac.uk/pdbsum/6hho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hho ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RIPK1_HUMAN RIPK1_HUMAN]] Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.<ref>PMID:11101870</ref> <ref>PMID:19524513</ref> <ref>PMID:19524512</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCII(hi)TNFalpha(+)IFNgamma(+) immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human PDA. Targeting RIP1 synergized with PD1-and inducible co-stimulator-based immunotherapies. Tumor-promoting effects of RIP1 were independent of its co-association with RIP3. Collectively, our work describes RIP1 as a checkpoint kinase governing tumor immunity.

-	~~Authors: Thorpe~~, J~~.H.~~, Harris, P.A.	+	RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer.,Wang W, Marinis JM, Beal AM, Savadkar S, Wu Y, Khan M, Taunk PS, Wu N, Su W, Wu J, Ahsan A, Kurz E, Chen T, Yaboh I, Li F, Gutierrez J, Diskin B, Hundeyin M, Reilly M, Lich JD, Harris PA, Mahajan MK, Thorpe JH, Nassau P, Mosley JE, Leinwand J, Kochen Rossi JA, Mishra A, Aykut B, Glacken M, Ochi A, Verma N, Kim JI, Vasudevaraja V, Adeegbe D, Almonte C, Bagdatlioglu E, Cohen DJ, Wong KK, Bertin J, Miller G Cancer Cell. 2018 Nov 12;34(5):757-774.e7. doi: 10.1016/j.ccell.2018.10.006. PMID:30423296<ref>PMID:30423296</ref>

-	~~Description: Crystal structure~~ of ~~RIP1~~ kinase ~~in complex with GSK547~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Thorpe, J.H]]	+	<div class="pdbe-citations 6hho" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Harris, P.A~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Harris, P A]]
		+	[[Category: Thorpe, J H]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transferase]]

OCA at 06:01, 12 September 2018

OCA — Wed, 12 Sep 2018 06:01:35 GMT

←Older revision		Revision as of 06:01, 12 September 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hho is ON HOLD	+	The entry 6hho is ON HOLD until Paper Publication

	Authors: Thorpe, J.H., Harris, P.A.		Authors: Thorpe, J.H., Harris, P.A.

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

OCA — Wed, 05 Sep 2018 08:46:27 GMT

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

←Older revision

Revision as of 08:46, 5 September 2018

OCA: New page: '''Unreleased structure''' The entry 6hho is ON HOLD Authors: Thorpe, J.H., Harris, P.A. Description: Crystal structure of RIP1 kinase in complex with GSK547 [[Category: Unreleased Str...

OCA — Wed, 05 Sep 2018 08:46:26 GMT

New page: '''Unreleased structure''' The entry 6hho is ON HOLD Authors: Thorpe, J.H., Harris, P.A. Description: Crystal structure of RIP1 kinase in complex with GSK547 [[Category: Unreleased Str...

New page

'''Unreleased structure'''

The entry 6hho is ON HOLD

Authors: Thorpe, J.H., Harris, P.A.

Description: Crystal structure of RIP1 kinase in complex with GSK547
[[Category: Unreleased Structures]]
[[Category: Thorpe, J.H]]
[[Category: Harris, P.A]]

6hho - Revision history

OCA at 06:51, 12 December 2018

OCA at 06:01, 12 September 2018

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

OCA: New page: '''Unreleased structure''' The entry 6hho is ON HOLD Authors: Thorpe, J.H., Harris, P.A. Description: Crystal structure of RIP1 kinase in complex with GSK547 [[Category: Unreleased Str...