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3wzu
From Proteopedia
(Difference between revisions)
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==THE STRUCTURE OF MAP2K7 IN COMPLEX WITH 5Z-7-oxozeaenol== | ==THE STRUCTURE OF MAP2K7 IN COMPLEX WITH 5Z-7-oxozeaenol== | ||
| - | <StructureSection load='3wzu' size='340' side='right'caption='[[3wzu]]' scene=''> | + | <StructureSection load='3wzu' size='340' side='right'caption='[[3wzu]], [[Resolution|resolution]] 3.01Å' 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=3WZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WZU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wzu]] 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=3WZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WZU FirstGlance]. <br> |
| - | </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=3wzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wzu OCA], [https://pdbe.org/3wzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wzu RCSB], [https://www.ebi.ac.uk/pdbsum/3wzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wzu ProSAT]</span></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]] 3.01Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1FM:(3S,5Z,8S,9S,11E)-8,9,16-TRIHYDROXY-14-METHOXY-3-METHYL-3,4,9,10-TETRAHYDRO-1H-2-BENZOXACYCLOTETRADECINE-1,7(8H)-DIONE'>1FM</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=3wzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wzu OCA], [https://pdbe.org/3wzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wzu RCSB], [https://www.ebi.ac.uk/pdbsum/3wzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wzu 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 == | ||
| + | 5Z-7-Oxozeaenol (5Z7O) is a covalent bonding inhibitor against the several protein kinases (e.g., ERK2 and TAK1) that possess a free cysteine at the gatekeeper-2 position. In addition to this cysteine, MAP2K7 has three other cysteine residues that are candidate for covalent bonding by the inhibitor 5Z7O. The crystal structure of the MAP2K7/5Z7O complex revealed that the inhibitor binds to MAP2K7 at a cysteine residue located at the end of the hinge region and not at the gatekeeper-2 residue. The structural insights into the interaction of 5Z7O with MAP2K7 should aid the development of 5Z7O derivatives with improved potency and selectivity. | ||
| + | |||
| + | 5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner.,Sogabe Y, Matsumoto T, Hashimoto T, Kirii Y, Sawa M, Kinoshita T Bioorg Med Chem Lett. 2014 Dec 13. pii: S0960-894X(14)01308-0. doi:, 10.1016/j.bmcl.2014.12.011. PMID:25529738<ref>PMID:25529738</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3wzu" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] | *[[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: Hashimoto Y]] | [[Category: Hashimoto Y]] | ||
Current revision
THE STRUCTURE OF MAP2K7 IN COMPLEX WITH 5Z-7-oxozeaenol
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