6qg7 - Revision history

OCA at 06:43, 29 May 2019

OCA — Wed, 29 May 2019 06:43:24 GMT

←Older revision		Revision as of 06:43, 29 May 2019
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	<StructureSection load='6qg7' size='340' side='right'caption='[[6qg7]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='6qg7' size='340' side='right'caption='[[6qg7]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qg7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QG7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QG7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qg7]] 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=6QG7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QG7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6HL:(R)-1-(3-(4-AMINO-3-(NAPHTHALEN-1-YL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL)PIPERIDIN-1-YL)PROP-2-EN-1-ONE'>6HL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6HL:(R)-1-(3-(4-AMINO-3-(NAPHTHALEN-1-YL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL)PIPERIDIN-1-YL)PROP-2-EN-1-ONE'>6HL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qfl\|6qfl]], [[6qfr\|6qfr]], [[6qft\|6qft]], [[6qg4\|6qg4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qfl\|6qfl]], [[6qfr\|6qfr]], [[6qft\|6qft]], [[6qg4\|6qg4]]</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='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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qg7 OCA], [http://pdbe.org/6qg7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qg7 RCSB], [http://www.ebi.ac.uk/pdbsum/6qg7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qg7 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=6qg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qg7 OCA], [http://pdbe.org/6qg7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qg7 RCSB], [http://www.ebi.ac.uk/pdbsum/6qg7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qg7 ProSAT]</span></td></tr>
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	== 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> [:]		[[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 ==
		+	Pyrazolopyrimidines are well established as covalent inhibitors of protein kinases such as the epidermal growth factor receptor (EGFR) or Bruton's tyrosine kinase (BTK) and we recently described their potential in targeting MKK7. Herein, we report the structure-activity relationship of pyrazolopyrimidine-based MKK7 inhibitors and solved sever-al complex crystal structures to gain insights into their binding mode. In addition, we present two structures of apo-MKK7, exhibiting a DFG-out and an unprecedented DFG-in/Leu-in conformation.
		+
		+	Characterization of Covalent Pyrazolopyrimidine-MKK7 Complexes and Report on a Unique DFG-in/Leu-in Conformation of the Mitogen Activated Protein Kinase Kinase 7 (MKK7).,Wolle P, Engel J, Smith S, Goebel L, Hennes E, Lategahn J, Rauh D J Med Chem. 2019 May 14. doi: 10.1021/acs.jmedchem.9b00472. PMID:31083997<ref>PMID:31083997</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qg7" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]

OCA at 06:58, 23 May 2019

OCA — Thu, 23 May 2019 06:58:42 GMT

←Older revision		Revision as of 06:58, 23 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qg7 is ~~ON HOLD~~	+	==Structure of the mitogen activated kinase kinase 7 in complex with pyrazolopyrimidine 1k==
-		+	<StructureSection load='6qg7' size='340' side='right'caption='[[6qg7]], [[Resolution\|resolution]] 2.10Å' scene=''>
-	~~Authors~~: ~~Wolle~~, P., ~~Mueller~~, M.P., ~~Rauh~~, D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qg7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QG7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QG7 FirstGlance]. <br>
-	~~Description~~: ~~Structure~~ of the ~~mitogen~~ activated kinase kinase 7 in ~~complex with pyrazolopyrimidine 1k~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6HL:(R)-1-(3-(4-AMINO-3-(NAPHTHALEN-1-YL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL)PIPERIDIN-1-YL)PROP-2-EN-1-ONE'>6HL</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qfl\|6qfl]], [[6qfr\|6qfr]], [[6qft\|6qft]], [[6qg4\|6qg4]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qg7 OCA], [http://pdbe.org/6qg7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qg7 RCSB], [http://www.ebi.ac.uk/pdbsum/6qg7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qg7 ProSAT]</span></td></tr>
		+	</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> [:]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mitogen-activated protein kinase kinase]]
		+	[[Category: Mueller, M P]]
		+	[[Category: Rauh, D]]
	[[Category: Wolle, P]]		[[Category: Wolle, P]]
-	[[Category: ~~Mueller, M.P~~]]	+	[[Category: Kinase]]
-	[[Category: ~~Rauh, D~~]]	+	[[Category: Mkk7]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

OCA: Protected "6qg7" [edit=sysop:move=sysop]

OCA — Wed, 16 Jan 2019 10:53:47 GMT

Protected "6qg7" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:53, 16 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qg7 is ON HOLD Authors: Wolle, P., Mueller, M.P., Rauh, D. Description: Structure of the mitogen activated kinase kinase 7 in complex with pyrazol...

OCA — Wed, 16 Jan 2019 10:53:46 GMT

New page: '''Unreleased structure''' The entry 6qg7 is ON HOLD Authors: Wolle, P., Mueller, M.P., Rauh, D. Description: Structure of the mitogen activated kinase kinase 7 in complex with pyrazol...

New page

'''Unreleased structure'''

The entry 6qg7 is ON HOLD

Authors: Wolle, P., Mueller, M.P., Rauh, D.

Description: Structure of the mitogen activated kinase kinase 7 in complex with pyrazolopyrimidine 1k
[[Category: Unreleased Structures]]
[[Category: Wolle, P]]
[[Category: Mueller, M.P]]
[[Category: Rauh, D]]