5jk3 - Revision history

OCA at 18:56, 20 September 2023

2023-09-20T18:56:25Z

←Older revision		Revision as of 18:56, 20 September 2023
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	<StructureSection load='5jk3' size='340' side='right'caption='[[5jk3]], [[Resolution\|resolution]] 2.37Å' scene=''>		<StructureSection load='5jk3' size='340' side='right'caption='[[5jk3]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5jk3]] 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=5JK3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5JK3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5jk3]] 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=5JK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JK3 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=6L4:~{N}~~-[2-[~~5-CHLORANYL-2-[(1-METHYLPYRAZOL-4-YL)AMINO~~]~~PYRIMIDIN-4-YL~~]~~OXYPHENYL]PROP-~~2~~-ENAMIDE'>6L4</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]] 2.371Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>TAB1, MAP3K7IP1 ([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=6L4:~{N}-[2-[5-CHLORANYL-2-[(1-METHYLPYRAZOL-4-YL)AMINO]PYRIMIDIN-4-YL]OXYPHENYL]PROP-2-ENAMIDE'>6L4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5jk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk3 OCA], [https://pdbe.org/5jk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jk3 RCSB], [https://www.ebi.ac.uk/pdbsum/5jk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk3 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=5jk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk3 OCA], [~~http~~://pdbe.org/5jk3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5jk3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5jk3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk3 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>	+	[https://www.uniprot.org/uniprot/TAB1_HUMAN TAB1_HUMAN] May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.<ref>PMID:16879102</ref> [https://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase kinase kinase]]~~	+	[[Category: Gurbani D]]
-	[[Category: Gurbani, D]]	+	[[Category: Westover KD]]
-	[[Category: Westover~~, K D]]~~	+
-	~~[[Category: Mitogen activated protein kinase kinase kinase 7]]~~	+
-	~~[[Category: Serine/threonine kinase which act as essential component of the map kinase signal transduction pathway]]~~	+
-	~~[[Category: Tgf-beta activated kinase 1 and map3k7-binding protein 1 chimera]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:07, 8 January 2020

2020-01-08T08:07:28Z

←Older revision		Revision as of 08:07, 8 January 2020
Line 1:		Line 1:

	==Crystal structure of TL11-128 bound to TAK1-TAB1==		==Crystal structure of TL11-128 bound to TAK1-TAB1==
-	<StructureSection load='5jk3' size='340' side='right' caption='[[5jk3]], [[Resolution\|resolution]] 2.37Å' scene=''>	+	<StructureSection load='5jk3' size='340' side='right'caption='[[5jk3]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5jk3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JK3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5jk3]] 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=5JK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JK3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6L4:~{N}-[2-[5-CHLORANYL-2-[(1-METHYLPYRAZOL-4-YL)AMINO]PYRIMIDIN-4-YL]OXYPHENYL]PROP-2-ENAMIDE'>6L4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6L4:~{N}-[2-[5-CHLORANYL-2-[(1-METHYLPYRAZOL-4-YL)AMINO]PYRIMIDIN-4-YL]OXYPHENYL]PROP-2-ENAMIDE'>6L4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TAB1, MAP3K7IP1 ([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=5jk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk3 OCA], [http://pdbe.org/5jk3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jk3 RCSB], [http://www.ebi.ac.uk/pdbsum/5jk3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk3 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=5jk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk3 OCA], [http://pdbe.org/5jk3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jk3 RCSB], [http://www.ebi.ac.uk/pdbsum/5jk3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk3 ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Gurbani, D]]		[[Category: Gurbani, D]]

OCA at 17:40, 10 March 2017

2017-03-10T17:40:34Z

←Older revision		Revision as of 17:40, 10 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5jk3 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of TL11-128 bound to TAK1-TAB1==
		+	<StructureSection load='5jk3' size='340' side='right' caption='[[5jk3]], [[Resolution\|resolution]] 2.37Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5jk3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JK3 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6L4:~{N}-[2-[5-CHLORANYL-2-[(1-METHYLPYRAZOL-4-YL)AMINO]PYRIMIDIN-4-YL]OXYPHENYL]PROP-2-ENAMIDE'>6L4</scene></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=5jk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk3 OCA], [http://pdbe.org/5jk3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jk3 RCSB], [http://www.ebi.ac.uk/pdbsum/5jk3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk3 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	TAK1 (transforming growth factor-beta-activated kinase 1) is an essential intracellular mediator of cytokine and growth factor signaling and a potential therapeutic target for the treatment of immune diseases and cancer. Herein we report development of a series of 2,4-disubstituted pyrimidine covalent TAK1 inhibitors that target Cys174, a residue immediately adjacent to the 'DFG-motif' of the kinase activation loop. Co-crystal structures of TAK1 with candidate compounds enabled iterative rounds of structure-based design and biological testing to arrive at optimized compounds. Lead compounds such as 2 and 10 showed greater than 10-fold biochemical selectivity for TAK1 over the closely related kinases MEK1 and ERK1 which possess an equivalently positioned cysteine residue. These compounds are smaller, more easily synthesized, and exhibit a different spectrum of kinase selectivity relative to previously reported macrocyclic natural product TAK1 inhibitors such as 5Z-7-oxozeanol.

-	~~Authors: Gurbani~~, D., Westover, K.D.	+	Structure-guided development of covalent TAK1 inhibitors.,Tan L, Gurbani D, Weisberg EL, Hunter JC, Li L, Jones DS, Ficarro SB, Mowafy S, Tam CP, Rao S, Du G, Griffin JD, Sorger PK, Marto JA, Westover KD, Gray NS Bioorg Med Chem. 2017 Feb 1;25(3):838-846. doi: 10.1016/j.bmc.2016.11.035. Epub, 2016 Dec 9. PMID:28011204<ref>PMID:28011204</ref>

-	~~Description: Crystal structure~~ of ~~TL11~~-~~128 bound to TAK1~~-~~TAB1~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5jk3" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Gurbani, D]]		[[Category: Gurbani, D]]
-	[[Category: Westover, K.D]]	+	[[Category: Westover, K D]]
		+	[[Category: Mitogen activated protein kinase kinase kinase 7]]
		+	[[Category: Serine/threonine kinase which act as essential component of the map kinase signal transduction pathway]]
		+	[[Category: Tgf-beta activated kinase 1 and map3k7-binding protein 1 chimera]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 12:38, 10 August 2016

2016-08-10T12:38:48Z

←Older revision		Revision as of 12:38, 10 August 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5jk3 is ON HOLD	+	The entry 5jk3 is ON HOLD until Paper Publication

	Authors: Gurbani, D., Westover, K.D.		Authors: Gurbani, D., Westover, K.D.

OCA: Protected "5jk3" [edit=sysop:move=sysop]

2016-05-11T02:11:38Z

Protected "5jk3" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:11, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5jk3 is ON HOLD Authors: Gurbani, D., Westover, K.D. Description: Crystal structure of TL11-128 bound to TAK1-TAB1 [[Category: Unreleased Structure...

2016-05-11T02:11:37Z

New page: '''Unreleased structure''' The entry 5jk3 is ON HOLD Authors: Gurbani, D., Westover, K.D. Description: Crystal structure of TL11-128 bound to TAK1-TAB1 [[Category: Unreleased Structure...

New page

'''Unreleased structure'''

The entry 5jk3 is ON HOLD

Authors: Gurbani, D., Westover, K.D.

Description: Crystal structure of TL11-128 bound to TAK1-TAB1
[[Category: Unreleased Structures]]
[[Category: Gurbani, D]]
[[Category: Westover, K.D]]