6yg0 - Revision history

OCA at 13:26, 24 January 2024

OCA — Wed, 24 Jan 2024 13:26:09 GMT

←Older revision		Revision as of 13:26, 24 January 2024
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	<StructureSection load='6yg0' size='340' side='right'caption='[[6yg0]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6yg0' size='340' side='right'caption='[[6yg0]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6yg0]] 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=6YG0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6YG0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yg0]] 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=6YG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YG0 FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>MAP2K7, JNKK2, MEK7, MKK7, PRKMK7, SKK4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</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]] 2Å</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 Mitogen-activated protein kinase kinase]~~, ~~with EC number~~ [~~http://www.brenda-enzymes.info/php/result_flat.php4?ecno=~~2~~.7.12.2 2.7.12.2] </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=6yg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yg0 OCA], [https://pdbe.org/6yg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yg0 RCSB], [https://www.ebi.ac.uk/pdbsum/6yg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yg0 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=6yg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yg0 OCA], [~~http~~://pdbe.org/6yg0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6yg0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6yg0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6yg0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MP2K7_HUMAN MP2K7_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.<ref>PMID:9372971</ref> <ref>PMID:9312068</ref> <ref>PMID:9535930</ref> [:]	+	[https://www.uniprot.org/uniprot/MP2K7_HUMAN MP2K7_HUMAN] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.<ref>PMID:9372971</ref> <ref>PMID:9312068</ref> <ref>PMID:9535930</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]]~~	+	[[Category: Chaikuad A]]
-	[[Category: Chaikuad, A]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+
-	~~[[Category: Structural genomic]]~~	+
-	~~[[Category: Jnk signaling]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Map2k]]~~	+
-	~~[[Category: Map2k7]]~~	+
-	~~[[Category: Mek]]~~	+
-	~~[[Category: Mek7]]~~	+
-	~~[[Category: Mkk7]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 20:52, 28 October 2020

OCA — Wed, 28 Oct 2020 20:52:37 GMT

←Older revision		Revision as of 20:52, 28 October 2020
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	</div>		</div>
	<div class="pdbe-citations 6yg0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6yg0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase kinase 3D structures\|Mitogen-activated protein kinase kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:11, 2 September 2020

OCA — Wed, 02 Sep 2020 07:11:56 GMT

←Older revision		Revision as of 07:11, 2 September 2020
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	==Crystal structure of S287D,T291D MKK7 (MAP2K7), apo form==		==Crystal structure of S287D,T291D MKK7 (MAP2K7), apo form==
-	<StructureSection load='6yg0' size='340' side='right'caption='[[6yg0]]' scene=''>	+	<StructureSection load='6yg0' size='340' side='right'caption='[[6yg0]], [[Resolution\|resolution]] 2.00Å' 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=6YG0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YG0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yg0]] 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=6YG0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YG0 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=6yg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yg0 OCA], [http://pdbe.org/6yg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yg0 RCSB], [http://www.ebi.ac.uk/pdbsum/6yg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yg0 ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP2K7, JNKK2, MEK7, MKK7, PRKMK7, SKK4 ([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 Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=6yg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yg0 OCA], [http://pdbe.org/6yg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yg0 RCSB], [http://www.ebi.ac.uk/pdbsum/6yg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yg0 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MP2K7_HUMAN MP2K7_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.<ref>PMID:9372971</ref> <ref>PMID:9312068</ref> <ref>PMID:9535930</ref> [:]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	MKK7 (MEK7) is a key regulator of the JNK stress signaling pathway and targeting MKK7 has been proposed as a chemotherapeutic strategy. Detailed understanding of the MKK7 structure and factors that affect its activity is therefore of critical importance. Here, we present a comprehensive set of MKK7 crystal structures revealing insights into catalytic domain plasticity and the role of the N-terminal regulatory helix, conserved in all MAP2Ks, mediating kinase activation. Crystal structures harboring this regulatory helix revealed typical structural features of active kinase, providing exclusively a first model of the MAP2K active state. A small-molecule screening campaign yielded multiple scaffolds, including type II irreversible inhibitors a binding mode that has not been reported previously. We also observed an unprecedented allosteric pocket located in the N-terminal lobe for the approved drug ibrutinib. Collectively, our structural and functional data expand and provide alternative targeting strategies for this important MAP2K kinase.
		+
		+	Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities.,Schroder M, Tan L, Wang J, Liang Y, Gray NS, Knapp S, Chaikuad A Cell Chem Biol. 2020 Aug 4. pii: S2451-9456(20)30287-7. doi:, 10.1016/j.chembiol.2020.07.014. PMID:32783966<ref>PMID:32783966</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6yg0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chaikuad A]]	+	[[Category: Mitogen-activated protein kinase kinase]]
-	[[Category: Knapp S]]	+	[[Category: Chaikuad, A]]
		+	[[Category: Knapp, S]]
		+	[[Category: Structural genomic]]
		+	[[Category: Jnk signaling]]
		+	[[Category: Kinase]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Map2k]]
		+	[[Category: Map2k7]]
		+	[[Category: Mek]]
		+	[[Category: Mek7]]
		+	[[Category: Mkk7]]
		+	[[Category: Sgc]]
		+	[[Category: Transferase]]

OCA at 09:50, 12 August 2020

OCA — Wed, 12 Aug 2020 09:50:01 GMT

←Older revision		Revision as of 09:50, 12 August 2020
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-	'''Unreleased structure'''

-	~~The entry 6yg0 is ON HOLD until Paper Publication~~	+	==Crystal structure of S287D,T291D MKK7 (MAP2K7), apo form==
-		+	<StructureSection load='6yg0' size='340' side='right'caption='[[6yg0]]' scene=''>
-	~~Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YG0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YG0 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of S287D,T291D MKK7 (MAP2K7), apo form	+	</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=6yg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yg0 OCA], [http://pdbe.org/6yg0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yg0 RCSB], [http://www.ebi.ac.uk/pdbsum/6yg0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yg0 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Chaikuad~~, A]]	+	__TOC__
-	[[Category: ~~Knapp, S~~]]	+	</StructureSection>
-	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Large Structures]]
		+	[[Category: Chaikuad A]]
		+	[[Category: Knapp S]]

OCA at 05:42, 8 April 2020

OCA — Wed, 08 Apr 2020 05:42:22 GMT

←Older revision		Revision as of 05:42, 8 April 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6yg0 is ON HOLD	+	The entry 6yg0 is ON HOLD until Paper Publication

	Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)		Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)

OCA: Protected "6yg0" [edit=sysop:move=sysop]

OCA — Wed, 01 Apr 2020 07:49:17 GMT

Protected "6yg0" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:49, 1 April 2020

OCA: New page: '''Unreleased structure''' The entry 6yg0 is ON HOLD Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of S287D,T291D MKK7 (MAP2K7),...

OCA — Wed, 01 Apr 2020 07:49:15 GMT

New page: '''Unreleased structure''' The entry 6yg0 is ON HOLD Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of S287D,T291D MKK7 (MAP2K7),...

New page

'''Unreleased structure'''

The entry 6yg0 is ON HOLD

Authors: Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of S287D,T291D MKK7 (MAP2K7), apo form
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Knapp, S]]
[[Category: Structural Genomics Consortium (Sgc)]]