5b2k

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'''Unreleased structure'''
 
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The entry 5b2k is ON HOLD until Paper Publication
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==A crucial role of Cys218 in the stabilization of an unprecedented auto-inhibition form of MAP2K7==
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<StructureSection load='5b2k' size='340' side='right'caption='[[5b2k]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5b2k]] 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=5B2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B2K FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5b2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2k OCA], [https://pdbe.org/5b2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b2k RCSB], [https://www.ebi.ac.uk/pdbsum/5b2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b2k ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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> [:]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mitogen-activated protein kinase kinase 7 (MAP2K7) is an indispensable kinase of the c-Jun N-terminal kinase signal cascade and is rigorously regulated via phosphorylation. To investigate the regulatory mechanism of the inactive non-phosphorylated state of MAP2K7, the crystal structures of the wild-type and C218S mutant were solved. The wild-type apo-structure revealed an unprecedented auto-inhibition form that occluded the ATP site. This closed form was configured by the n-sigma* interaction of Cys218, a non-conserved residue among the MAP2K family kinases, with Gly145 in the glycine-rich loop. The interaction was unaltered in the presence of an ATP analog, whereas the C218S mutation precluded the closed configuration. These structural insights are potentially valuable for drug discovery of highly selective MAP2K7 inhibitors.
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Authors: Sogabe, Y., Hashimoto, T., Matsumoto, T., Kirii, Y., Sawa, M., Kinoshita, T.
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A crucial role of Cys218 in configuring an unprecedented auto-inhibition form of MAP2K7.,Sogabe Y, Hashimoto T, Matsumoto T, Kirii Y, Sawa M, Kinoshita T Biochem Biophys Res Commun. 2016 Apr 29;473(2):476-81. doi:, 10.1016/j.bbrc.2016.03.036. Epub 2016 Mar 15. PMID:26987717<ref>PMID:26987717</ref>
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Description: A crucial role of Cys218 in the stabilization of an unprecedented auto-inhibition form of MAP2K7
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Kinoshita, T]]
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<div class="pdbe-citations 5b2k" style="background-color:#fffaf0;"></div>
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[[Category: Matsumoto, T]]
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[[Category: Hashimoto, T]]
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==See Also==
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[[Category: Kirii, Y]]
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*[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]]
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[[Category: Sogabe, Y]]
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== References ==
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[[Category: Sawa, M]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Hashimoto T]]
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[[Category: Kinoshita T]]
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[[Category: Kirii Y]]
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[[Category: Matsumoto T]]
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[[Category: Sawa M]]
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[[Category: Sogabe Y]]

Current revision

A crucial role of Cys218 in the stabilization of an unprecedented auto-inhibition form of MAP2K7

PDB ID 5b2k

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