5ko1 - Revision history

OCA at 10:04, 27 September 2023

OCA — Wed, 27 Sep 2023 10:04:39 GMT

←Older revision		Revision as of 10:04, 27 September 2023
Line 3:		Line 3:
	<StructureSection load='5ko1' size='340' side='right'caption='[[5ko1]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='5ko1' size='340' side='right'caption='[[5ko1]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ko1]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KO1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5KO1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ko1]] is a 1 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=5KO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KO1 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=6UY:[(1~{R})-2~~-[~~(4-FLUOROPHENYL)AMINO~~]~~-2-OXIDANYLIDENE-1-PHENYL-ETHYL~~]~~+3-AZANYLPYRAZINE-~~2~~-CARBOXYLATE'>6UY</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]] 2.16Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5knj\|5knj]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6UY:[(1~{R})-2-[(4-FLUOROPHENYL)AMINO]-2-OXIDANYLIDENE-1-PHENYL-ETHYL]+3-AZANYLPYRAZINE-2-CARBOXYLATE'>6UY</scene></td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~"><b>[[~~Gene\|Gene:~~]]~~</b~~></td>~~<td class="sblockDat">MLKL ([http://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=5ko1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko1 OCA], [https://pdbe.org/5ko1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ko1 RCSB], [https://www.ebi.ac.uk/pdbsum/5ko1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko1 ProSAT]</span></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=5ko1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko1 OCA], [~~http~~://pdbe.org/5ko1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ko1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ko1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko1 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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 24:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Marcotte~~, D J]]~~	+	[[Category: Marcotte DJ]]
-	~~[[Category: Membrane proteins-inhibitor complex]]~~	+
-	~~[[Category: Pseudokinase domain mlkl type1 inhibitor~~]]	+

OCA at 06:29, 5 August 2020

OCA — Wed, 05 Aug 2020 06:29:30 GMT

←Older revision		Revision as of 06:29, 5 August 2020
Line 1:		Line 1:

	==Pseudokinase Domain of MLKL bound to Compound 4.==		==Pseudokinase Domain of MLKL bound to Compound 4.==
-	<StructureSection load='5ko1' size='340' side='right' caption='[[5ko1]], [[Resolution\|resolution]] 2.16Å' scene=''>	+	<StructureSection load='5ko1' size='340' side='right'caption='[[5ko1]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ko1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KO1 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5KO1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ko1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KO1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KO1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6UY:[(1~{R})-2-[(4-FLUOROPHENYL)AMINO]-2-OXIDANYLIDENE-1-PHENYL-ETHYL]+3-AZANYLPYRAZINE-2-CARBOXYLATE'>6UY</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6UY:[(1~{R})-2-[(4-FLUOROPHENYL)AMINO]-2-OXIDANYLIDENE-1-PHENYL-ETHYL]+3-AZANYLPYRAZINE-2-CARBOXYLATE'>6UY</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5knj\|5knj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5knj\|5knj]]</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=5ko1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko1 OCA], [http://pdbe.org/5ko1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ko1 RCSB], [http://www.ebi.ac.uk/pdbsum/5ko1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko1 ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MLKL ([http://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'>[http://proteopedia.org/fgij/fg.htm?mol=5ko1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko1 OCA], [http://pdbe.org/5ko1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ko1 RCSB], [http://www.ebi.ac.uk/pdbsum/5ko1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Marcotte, D J]]		[[Category: Marcotte, D J]]
	[[Category: Membrane proteins-inhibitor complex]]		[[Category: Membrane proteins-inhibitor complex]]
	[[Category: Pseudokinase domain mlkl type1 inhibitor]]		[[Category: Pseudokinase domain mlkl type1 inhibitor]]

OCA at 03:28, 10 December 2016

OCA — Sat, 10 Dec 2016 03:28:58 GMT

←Older revision		Revision as of 03:28, 10 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ko1 is ~~ON HOLD~~	+	==Pseudokinase Domain of MLKL bound to Compound 4.==
		+	<StructureSection load='5ko1' size='340' side='right' caption='[[5ko1]], [[Resolution\|resolution]] 2.16Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ko1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KO1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KO1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6UY:[(1~{R})-2-[(4-FLUOROPHENYL)AMINO]-2-OXIDANYLIDENE-1-PHENYL-ETHYL]+3-AZANYLPYRAZINE-2-CARBOXYLATE'>6UY</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5knj\|5knj]]</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=5ko1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko1 OCA], [http://pdbe.org/5ko1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ko1 RCSB], [http://www.ebi.ac.uk/pdbsum/5ko1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko1 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 ==
		+	MLKL is a pore forming pseudokinase involved in the final stage of necroptosis, a form of programmed cell death. Its phosphorylation by RIPK3 is necessary for triggering necroptosis but not for triggering apoptosis, which makes it a unique target for pharmacological inhibition to block necroptotic cell death. This mechanism has been described as playing a role in disease progression in neurodegenerative and inflammatory diseases. A type II kinase inhibitor (cpd 1) has been described that reportedly binds to the MLKL pseudokinase domain and prevents necroptosis. Here we describe five compounds that bind to the MLKL ATP-binding site, however the four MLKL-selective compounds have no activity in rescuing cells from necroptosis. We use kinase selectivity panels, crystallography and a new conformationally sensitive method of measuring protein conformational changes (SHG) to confirm that the one previously reported compound that can rescue cells (cpd 1) is a non-selective type II inhibitor that also inhibits the upstream kinase RIPK1. Although this compound can shift the GFE motif of the activation loop to an "out" position, the accessibility of the key residue Ser358 in the MLKL activation loop is not affected by compound binding to the MLKL active site. Our studies indicate that an ATP-pocket inhibitor of the MLKL pseudokinase domain does not have any impact on the necroptosis pathway, which is contrary to a previously reported study.

-	~~Authors: Marcotte~~, D.J.	+	ATP-Competitive MLKL Binders Have No Functional Impact on Necroptosis.,Ma B, Marcotte D, Paramasivam M, Michelsen K, Wang T, Bertolotti-Ciarlet A, Jones JH, Moree B, Butko M, Salafsky J, Sun X, McKee T, Silvian LF PLoS One. 2016 Nov 10;11(11):e0165983. doi: 10.1371/journal.pone.0165983., eCollection 2016. PMID:27832137<ref>PMID:27832137</ref>

-	~~Description: Pseudokinase Domain~~ of ~~MLKL bound to Compound 4~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Marcotte, D.J~~]]	+	<div class="pdbe-citations 5ko1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Marcotte, D J]]
		+	[[Category: Membrane proteins-inhibitor complex]]
		+	[[Category: Pseudokinase domain mlkl type1 inhibitor]]

OCA at 10:49, 21 September 2016

OCA — Wed, 21 Sep 2016 10:49:10 GMT

←Older revision		Revision as of 10:49, 21 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ko1 is ON HOLD ~~until Paper Publication~~	+	The entry 5ko1 is ON HOLD

	Authors: Marcotte, D.J.		Authors: Marcotte, D.J.

-	Description: Pseudokinase Domain of MLKL bound to Compound 1.	+	Description: Pseudokinase Domain of MLKL bound to Compound 4.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Marcotte, D.J]]		[[Category: Marcotte, D.J]]

OCA at 01:52, 4 August 2016

OCA — Thu, 04 Aug 2016 01:52:53 GMT

←Older revision		Revision as of 01:52, 4 August 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ko1 is ON HOLD	+	The entry 5ko1 is ON HOLD until Paper Publication

	Authors: Marcotte, D.J.		Authors: Marcotte, D.J.

OCA: Protected "5ko1" [edit=sysop:move=sysop]

OCA — Wed, 13 Jul 2016 00:38:10 GMT

Protected "5ko1" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:38, 13 July 2016

OCA: New page: '''Unreleased structure''' The entry 5ko1 is ON HOLD Authors: Marcotte, D.J. Description: Pseudokinase Domain of MLKL bound to Compound 1. Category: Unreleased Structures [[Categor...

OCA — Wed, 13 Jul 2016 00:38:09 GMT

New page: '''Unreleased structure''' The entry 5ko1 is ON HOLD Authors: Marcotte, D.J. Description: Pseudokinase Domain of MLKL bound to Compound 1. Category: Unreleased Structures [[Categor...

New page

'''Unreleased structure'''

The entry 5ko1 is ON HOLD

Authors: Marcotte, D.J.

Description: Pseudokinase Domain of MLKL bound to Compound 1.
[[Category: Unreleased Structures]]
[[Category: Marcotte, D.J]]