4y85 - Revision history

OCA at 11:30, 9 May 2024

2024-05-09T11:30:57Z

←Older revision		Revision as of 11:30, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</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]] 2.33Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [https://pdbe.org/4y85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [https://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [https://pdbe.org/4y85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [https://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:02, 3 May 2023

2023-05-03T08:02:27Z

←Older revision		Revision as of 08:02, 3 May 2023
Line 3:		Line 3:
	<StructureSection load='4y85' size='340' side='right'caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>		<StructureSection load='4y85' size='340' side='right'caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y83\|4y83]]</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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [https://pdbe.org/4y85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [https://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP3K8, COT, ESTF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [~~http~~://pdbe.org/4y85 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN]] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>	+	[https://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase kinase kinase]]~~	+	[[Category: Gutmann S]]
-	[[Category: Gutmann, S]]	+	[[Category: Hinniger A]]
-	[[Category: Hinniger, A]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Cot]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Map3k8]]~~	+
-	~~[[Category: Tpl-2]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:30, 24 April 2019

2019-04-24T07:30:32Z

←Older revision		Revision as of 07:30, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine==		==Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine==
-	<StructureSection load='4y85' size='340' side='right' caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>	+	<StructureSection load='4y85' size='340' side='right'caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>
Line 26:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Gutmann, S]]		[[Category: Gutmann, S]]

OCA at 05:46, 27 June 2018

2018-06-27T05:46:40Z

←Older revision		Revision as of 05:46, 27 June 2018
Line 3:		Line 3:
	<StructureSection load='4y85' size='340' side='right' caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>		<StructureSection load='4y85' size='340' side='right' caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4y85]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4y85]] is a 3 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=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y83\|4y83]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y83\|4y83]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP3K8, COT, ESTF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [http://pdbe.org/4y85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [http://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [http://pdbe.org/4y85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [http://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Gutmann, S]]		[[Category: Gutmann, S]]

OCA at 14:25, 29 March 2017

2017-03-29T14:25:39Z

←Older revision		Revision as of 14:25, 29 March 2017
Line 1:		Line 1:
		+
	==Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine==		==Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine==
	<StructureSection load='4y85' size='340' side='right' caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>		<StructureSection load='4y85' size='340' side='right' caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y83\|4y83]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y83\|4y83]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [http://www.ebi.ac.uk/pdbsum/4y85 PDBsum]</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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [http://pdbe.org/4y85 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [http://www.ebi.ac.uk/pdbsum/4y85 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y85 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4y85" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:29, 13 May 2015

2015-05-13T06:29:47Z

←Older revision		Revision as of 06:29, 13 May 2015
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN]] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>		[[http://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN]] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis (RA). Cancer Osaka Thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a Serine-Threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the X-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this publication reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low-molecular weight COT inhibitors.
		+
		+	The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold.,Gutmann S, Hinniger A, Fendrich G, Drueckes P, Antz S, Mattes H, Moebitz H, Ofner S, Schmiedeberg N, Stojanovic A, Rieffel S, Strauss A, Troxler T, Glatthar R, Sparrer H J Biol Chem. 2015 Apr 27. pii: jbc.M115.648097. PMID:25918157<ref>PMID:25918157</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:04, 6 May 2015

2015-05-06T13:04:03Z

←Older revision		Revision as of 13:04, 6 May 2015
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	==Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine==
-		+	<StructureSection load='4y85' size='340' side='right' caption='[[4y85]], [[Resolution\|resolution]] 2.33Å' scene=''>
-	~~The entry 4y85 is ON HOLD~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4y85]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y85 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y85 FirstGlance]. <br>
-	~~Authors: Gutmann, S., Hinniger, A.~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=499:5-[5-(1H-INDOL-3-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]-1,3,4-OXADIAZOL-2-AMINE'>499</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y83\|4y83]]</td></tr>
-	~~Description:~~ Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=4y85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y85 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y85 RCSB], [http://www.ebi.ac.uk/pdbsum/4y85 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN]] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Gutmann, S]]		[[Category: Gutmann, S]]
	[[Category: Hinniger, A]]		[[Category: Hinniger, A]]
		+	[[Category: Complex]]
		+	[[Category: Cot]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Map3k8]]
		+	[[Category: Tpl-2]]
		+	[[Category: Transferase]]

OCA at 09:10, 30 April 2015

2015-04-30T09:10:31Z

←Older revision		Revision as of 09:10, 30 April 2015
Line 5:		Line 5:
	Authors: Gutmann, S., Hinniger, A.		Authors: Gutmann, S., Hinniger, A.

-	Description:	+	Description: Crystal structure of COT kinase domain in complex with 5-(5-(1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Gutmann, S]]		[[Category: Gutmann, S]]
	[[Category: Hinniger, A]]		[[Category: Hinniger, A]]

OCA: Protected "4y85" [edit=sysop:move=sysop]

2015-02-25T12:47:43Z

Protected "4y85" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:47, 25 February 2015

OCA: New page: '''Unreleased structure''' The entry 4y85 is ON HOLD Authors: Gutmann, S., Hinniger, A. Description: Category: Unreleased Structures Category: Gutmann, S [[Category: Hinniger,...

2015-02-25T12:47:42Z

New page: '''Unreleased structure''' The entry 4y85 is ON HOLD Authors: Gutmann, S., Hinniger, A. Description: Category: Unreleased Structures Category: Gutmann, S [[Category: Hinniger,...

New page

'''Unreleased structure'''

The entry 4y85 is ON HOLD

Authors: Gutmann, S., Hinniger, A.

Description:
[[Category: Unreleased Structures]]
[[Category: Gutmann, S]]
[[Category: Hinniger, A]]