7cbx
From Proteopedia
(Difference between revisions)
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==Crystal structure of MAP2K7 complexed with a covalent inhibitor 12== | ==Crystal structure of MAP2K7 complexed with a covalent inhibitor 12== | ||
| - | <StructureSection load='7cbx' size='340' side='right'caption='[[7cbx]]' scene=''> | + | <StructureSection load='7cbx' size='340' side='right'caption='[[7cbx]], [[Resolution|resolution]] 2.06Å' 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=7CBX OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[7cbx]] 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=7CBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CBX FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.061Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FU6:3-(1H-indazol-3-yl)-5-(prop-2-enoylamino)-N-prop-2-ynyl-benzamide'>FU6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7cbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cbx OCA], [https://pdbe.org/7cbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cbx RCSB], [https://www.ebi.ac.uk/pdbsum/7cbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cbx ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Mitogen-activated protein kinase kinase 7 (MAP2K7) in the c-Jun N-terminal kinase signal cascade is an attractive drug target for a variety of diseases. The selectivity of MAP2K7 inhibitors against off-target kinases is a major barrier in drug development. We report a crystal structure of MAP2K7 complexed with a potent covalent inhibitor bearing an acrylamide moiety as an electrophile, which discloses a structural basis for producing selective and potent MAP2K7 inhibitors. | ||
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| + | Structural basis for producing selective MAP2K7 inhibitors.,Murakawa Y, Valter S, Barr H, London N, Kinoshita T Bioorg Med Chem Lett. 2020 Sep 12;30(22):127546. doi: 10.1016/j.bmcl.2020.127546. PMID:32931911<ref>PMID:32931911</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7cbx" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Kinoshita T]] | [[Category: Kinoshita T]] | ||
[[Category: Murakawa Y]] | [[Category: Murakawa Y]] | ||
Current revision
Crystal structure of MAP2K7 complexed with a covalent inhibitor 12
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