6o5z - Revision history

OCA at 07:05, 11 October 2023

OCA — Wed, 11 Oct 2023 07:05:15 GMT

←Older revision		Revision as of 07:05, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6o5z' size='340' side='right'caption='[[6o5z]], [[Resolution\|resolution]] 2.29Å' scene=''>		<StructureSection load='6o5z' size='340' side='right'caption='[[6o5z]], [[Resolution\|resolution]] 2.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o5z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O5Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o5z]] 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=6O5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O5Z FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LN4:1-[2-fluoranyl-5-(trifluoromethyl)phenyl]-3-[4-[methyl-[2-[(3-sulfamoylphenyl)amino]pyrimidin-4-yl]amino]phenyl]urea'>LN4</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]] 2.285Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MLKL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LN4:1-[2-fluoranyl-5-(trifluoromethyl)phenyl]-3-[4-[methyl-[2-[(3-sulfamoylphenyl)amino]pyrimidin-4-yl]amino]phenyl]urea'>LN4</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=6o5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5z OCA], [https://pdbe.org/6o5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o5z RCSB], [https://www.ebi.ac.uk/pdbsum/6o5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5z 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=6o5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5z OCA], [https://pdbe.org/6o5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o5z RCSB], [https://www.ebi.ac.uk/pdbsum/6o5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5z ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MLKL_HUMAN MLKL_HUMAN]] Required for the execution of programmed necrosis.<ref>PMID:22265414</ref>	+	[https://www.uniprot.org/uniprot/MLKL_HUMAN MLKL_HUMAN] Required for the execution of programmed necrosis.<ref>PMID:22265414</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cowan~~, A D~~]]	+	[[Category: Cowan AD]]
-	[[Category: Czabotar~~, P E~~]]	+	[[Category: Czabotar PE]]
-	[[Category: Lessene~~, G L~~]]	+	[[Category: Lessene GL]]
-	[[Category: Murphy~~, J M~~]]	+	[[Category: Murphy JM]]
-	[[Category: Pierotti~~, C L]]~~	+	[[Category: Pierotti CL]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Necroptosis]]~~	+
-	~~[[Category: Pseudokinase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 14:54, 3 March 2021

OCA — Wed, 03 Mar 2021 14:54:34 GMT

←Older revision		Revision as of 14:54, 3 March 2021
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	==Crystal Structure of the human MLKL pseudokinase domain bound to compound 2==		==Crystal Structure of the human MLKL pseudokinase domain bound to compound 2==
-	<StructureSection load='6o5z' size='340' side='right'caption='[[6o5z]]' scene=''>	+	<StructureSection load='6o5z' size='340' side='right'caption='[[6o5z]], [[Resolution\|resolution]] 2.29Å' 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=6O5Z OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6O5Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o5z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O5Z FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6o5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5z OCA], [~~http~~://pdbe.org/6o5z PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6o5z RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6o5z PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5z 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LN4:1-[2-fluoranyl-5-(trifluoromethyl)phenyl]-3-[4-[methyl-[2-[(3-sulfamoylphenyl)amino]pyrimidin-4-yl]amino]phenyl]urea'>LN4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MLKL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6o5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5z OCA], [https://pdbe.org/6o5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o5z RCSB], [https://www.ebi.ac.uk/pdbsum/6o5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5z ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/MLKL_HUMAN MLKL_HUMAN]] Required for the execution of programmed necrosis.<ref>PMID:22265414</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Necroptosis is an inflammatory form of programmed cell death that has been implicated in various human diseases. Compound 2 is a more potent analogue of the published compound 1 and inhibits necroptosis in human and murine cells at nanomolar concentrations. Several target engagement strategies were employed, including cellular thermal shift assays (CETSA) and diazirine-mediated photoaffinity labeling via a bifunctional photoaffinity probe derived from compound 2. These target engagement studies demonstrate that compound 2 binds to all three necroptotic effector proteins (mixed lineage kinase domain-like protein (MLKL), receptor-interacting serine/threonine protein kinase 1 (RIPK1) and receptor-interacting serine/threonine protein kinase 3 (RIPK3)) at different levels in vitro and in cells. Compound 2 also shows efficacy in vivo in a murine model of systemic inflammatory response syndrome (SIRS).
		+
		+	Potent Inhibition of Necroptosis by Simultaneously Targeting Multiple Effectors of the Pathway.,Pierotti CL, Tanzer MC, Jacobsen AV, Hildebrand JM, Garnier JM, Sharma P, Lucet IS, Cowan AD, Kersten WJA, Luo MX, Liang LY, Fitzgibbon C, Garnish SE, Hempel A, Nachbur U, Huang DCS, Czabotar PE, Silke J, van Delft MF, Murphy JM, Lessene G ACS Chem Biol. 2020 Oct 16;15(10):2702-2713. doi: 10.1021/acschembio.0c00482., Epub 2020 Sep 22. PMID:32902249<ref>PMID:32902249</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6o5z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cowan AD]]	+	[[Category: Cowan, A D]]
-	[[Category: Czabotar PE]]	+	[[Category: Czabotar, P E]]
-	[[Category: Lessene GL]]	+	[[Category: Lessene, G L]]
-	[[Category: Murphy JM]]	+	[[Category: Murphy, J M]]
-	[[Category: Pierotti CL]]	+	[[Category: Pierotti, C L]]
		+	[[Category: Inhibitor]]
		+	[[Category: Necroptosis]]
		+	[[Category: Pseudokinase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:46, 16 September 2020

OCA — Wed, 16 Sep 2020 09:46:11 GMT

←Older revision		Revision as of 09:46, 16 September 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6o5z is ~~ON HOLD until Paper Publication~~	+	==Crystal Structure of the human MLKL pseudokinase domain bound to compound 2==
-		+	<StructureSection load='6o5z' size='340' side='right'caption='[[6o5z]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5Z OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6O5Z FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6o5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5z OCA], [http://pdbe.org/6o5z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o5z RCSB], [http://www.ebi.ac.uk/pdbsum/6o5z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5z ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Cowan AD]]
		+	[[Category: Czabotar PE]]
		+	[[Category: Lessene GL]]
		+	[[Category: Murphy JM]]
		+	[[Category: Pierotti CL]]

OCA: Protected "6o5z" [edit=sysop:move=sysop]

OCA — Wed, 13 Mar 2019 10:15:36 GMT

Protected "6o5z" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:15, 13 March 2019

OCA: New page: '''Unreleased structure''' The entry 6o5z is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 13 Mar 2019 10:15:34 GMT

New page: '''Unreleased structure''' The entry 6o5z is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6o5z is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]