6hx1 - Revision history

OCA at 11:41, 24 January 2024

OCA — Wed, 24 Jan 2024 11:41:39 GMT

←Older revision		Revision as of 11:41, 24 January 2024
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	<StructureSection load='6hx1' size='340' side='right'caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>		<StructureSection load='6hx1' size='340' side='right'caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hx1]] 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=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hx1]] 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=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GXK:6-chloranyl-~{N}-(cyclopropylmethyl)-3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-8-amine'>GXK</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]] 2.14Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERN1, IRE1 ([http://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=GXK:6-chloranyl-~{N}-(cyclopropylmethyl)-3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-8-amine'>GXK</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=6hx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hx1 OCA], [~~http~~://pdbe.org/6hx1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6hx1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6hx1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6hx1 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=6hx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hx1 OCA], [https://pdbe.org/6hx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hx1 RCSB], [https://www.ebi.ac.uk/pdbsum/6hx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hx1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ERN1_HUMAN ERN1_HUMAN]] Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.<ref>PMID:9637683</ref> <ref>PMID:11175748</ref> <ref>PMID:12637535</ref> [UniProtKB:Q9EQY0]	+	[https://www.uniprot.org/uniprot/ERN1_HUMAN ERN1_HUMAN] Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.<ref>PMID:9637683</ref> <ref>PMID:11175748</ref> <ref>PMID:12637535</ref> [UniProtKB:Q9EQY0]
	<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 6hx1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6hx1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ire1\|Ire1]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Augustin~~, M A~~]]	+	[[Category: Augustin MA]]
-	[[Category: Bayliss, R]]	+	[[Category: Bayliss R]]
-	[[Category: Collins, I]]	+	[[Category: Collins I]]
-	[[Category: Krapp, S]]	+	[[Category: Krapp S]]
-	~~[[Category: Ire1 kinase]]~~	+
-	~~[[Category: Proteros biostructures gmbh]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:30, 30 October 2019

OCA — Wed, 30 Oct 2019 09:30:57 GMT

←Older revision		Revision as of 09:30, 30 October 2019
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	<StructureSection load='6hx1' size='340' side='right'caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>		<StructureSection load='6hx1' size='340' side='right'caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hx1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hx1]] 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=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GXK:6-chloranyl-~{N}-(cyclopropylmethyl)-3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-8-amine'>GXK</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GXK:6-chloranyl-~{N}-(cyclopropylmethyl)-3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-8-amine'>GXK</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERN1, IRE1 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hx1 OCA], [http://pdbe.org/6hx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hx1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hx1 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=6hx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hx1 OCA], [http://pdbe.org/6hx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hx1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hx1 ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Augustin, M A]]		[[Category: Augustin, M A]]

OCA at 07:05, 27 March 2019

OCA — Wed, 27 Mar 2019 07:05:04 GMT

←Older revision		Revision as of 07:05, 27 March 2019
Line 1:		Line 1:

	==IRE1 ALPHA IN COMPLEX WITH imidazo[1,2-b]pyridazin-8-amine compound 2==		==IRE1 ALPHA IN COMPLEX WITH imidazo[1,2-b]pyridazin-8-amine compound 2==
-	<StructureSection load='6hx1' size='340' side='right' caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>	+	<StructureSection load='6hx1' size='340' side='right'caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6hx1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6hx1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Augustin, M A]]		[[Category: Augustin, M A]]
	[[Category: Bayliss, R]]		[[Category: Bayliss, R]]

OCA at 15:23, 27 February 2019

OCA — Wed, 27 Feb 2019 15:23:49 GMT

←Older revision		Revision as of 15:23, 27 February 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6hx1 is ~~ON HOLD until Paper~~ Publication	+	==IRE1 ALPHA IN COMPLEX WITH imidazo[1,2-b]pyridazin-8-amine compound 2==
		+	<StructureSection load='6hx1' size='340' side='right' caption='[[6hx1]], [[Resolution\|resolution]] 2.14Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hx1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HX1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GXK:6-chloranyl-~{N}-(cyclopropylmethyl)-3-(2~{H}-indazol-5-yl)imidazo[1,2-b]pyridazin-8-amine'>GXK</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=6hx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hx1 OCA], [http://pdbe.org/6hx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hx1 RCSB], [http://www.ebi.ac.uk/pdbsum/6hx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hx1 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ERN1_HUMAN ERN1_HUMAN]] Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.<ref>PMID:9637683</ref> <ref>PMID:11175748</ref> <ref>PMID:12637535</ref> [UniProtKB:Q9EQY0]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A series of imidazo[1,2-b]pyridazin-8-amine kinase inhibitors was discovered to allosterically inhibit the endoribonuclease function of the dual kinase-endoribonuclease inositol-requiring enzyme 1alpha (IRE1alpha), a key component of the unfolded protein response in mammalian cells and a potential drug target in multiple human diseases. Inhibitor optimization gave compounds with high kinome selectivity that prevented endoplasmic reticulum stress-induced IRE1alpha oligomerization and phosphorylation, and inhibited endoribonuclease activity in human cells. X-ray crystallography showed the inhibitors to bind to a previously unreported and unusually disordered conformation of the IRE1alpha kinase domain that would be incompatible with back-to-back dimerization of the IRE1alpha protein and activation of the endoribonuclease function. These findings increase the repertoire of known IRE1alpha protein conformations and can guide the discovery of highly selective ligands for the IRE1alpha kinase site that allosterically inhibit the endoribonuclease.

-	~~Authors~~:	+	Binding to an unusual inactive kinase conformation by highly selective inhibitors of inositol-requiring enzyme 1alpha kinase-endoribonuclease.,Colombano G, Caldwell JJ, Matthews TP, Bhatia C, Joshi A, McHardy T, Mok NY, Newbatt Y, Pickard L, Strover J, Hedayat S, Walton MI, Myers S, Jones AM, Saville H, McAndrew C, Burke R, Eccles S, Davies F, Bayliss R, Collins I J Med Chem. 2019 Feb 19. doi: 10.1021/acs.jmedchem.8b01721. PMID:30779566<ref>PMID:30779566</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6hx1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Augustin, M A]]
		+	[[Category: Bayliss, R]]
		+	[[Category: Collins, I]]
		+	[[Category: Krapp, S]]
		+	[[Category: Ire1 kinase]]
		+	[[Category: Proteros biostructures gmbh]]
		+	[[Category: Transferase]]

OCA at 06:00, 30 January 2019

OCA — Wed, 30 Jan 2019 06:00:17 GMT

←Older revision		Revision as of 06:00, 30 January 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hx1 is ON HOLD	+	The entry 6hx1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6hx1" [edit=sysop:move=sysop]

OCA — Wed, 24 Oct 2018 04:13:12 GMT

Protected "6hx1" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:13, 24 October 2018

OCA: New page: '''Unreleased structure''' The entry 6hx1 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 24 Oct 2018 04:13:10 GMT

New page: '''Unreleased structure''' The entry 6hx1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6hx1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]