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6ib2
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6ib2 is ON HOLD Authors: Wolle, P., Hardick, J., Engel, J., Mueller, M.P., Rauh, D. Description: The structure of MKK7 in complex with the covalent...) |
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The structure of MKK7 in complex with the covalent 4-amino-pyrazolopyrimidine 4a== |
| + | <StructureSection load='6ib2' size='340' side='right'caption='[[6ib2]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ib2]] 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=6IB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IB2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=862:1-[(3~{R})-3-[4-azanyl-3-[1-(4-ethanoylphenyl)-1,2,3-triazol-4-yl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]propan-1-one'>862</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=6ib2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ib2 OCA], [https://pdbe.org/6ib2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ib2 RCSB], [https://www.ebi.ac.uk/pdbsum/6ib2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ib2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The protein kinase MKK7 is linked to neuronal development and the onset of cancer. The field, however, lacks high-quality functional probes that would allow for the dissection of its detailed functions. Against this background, we describe an effective covalent inhibitor of MKK7 based on the pyrazolopyrimidine scaffold. | ||
| - | + | Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors.,Wolle P, Hardick J, Cronin SJF, Engel J, Baumann M, Lategahn J, Penninger JM, Rauh D J Med Chem. 2019 Feb 21. doi: 10.1021/acs.jmedchem.9b00102. PMID:30768270<ref>PMID:30768270</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6ib2" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Mueller | + | ==See Also== |
| - | [[Category: Rauh | + | *[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hardick J]] | ||
| + | [[Category: Mueller MP]] | ||
| + | [[Category: Rauh D]] | ||
| + | [[Category: Wolle P]] | ||
Current revision
The structure of MKK7 in complex with the covalent 4-amino-pyrazolopyrimidine 4a
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