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5b2k

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Revision as of 10:01, 26 February 2020

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

Structural highlights

5b2k is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5b2m, 5b2l
Gene:	MAP2K7, JNKK2, MEK7, MKK7, PRKMK7, SKK4 (HUMAN)
Activity:	Mitogen-activated protein kinase kinase, with EC number 2.7.12.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] [:]

Publication Abstract from PubMed

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.

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu Z, Wu J, Jacinto E, Karin M. Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase. Mol Cell Biol. 1997 Dec;17(12):7407-16. PMID:9372971
↑ Lu X, Nemoto S, Lin A. Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38. J Biol Chem. 1997 Oct 3;272(40):24751-4. PMID:9312068
↑ Foltz IN, Gerl RE, Wieler JS, Luckach M, Salmon RA, Schrader JW. Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli. J Biol Chem. 1998 Apr 10;273(15):9344-51. PMID:9535930
↑ Sogabe Y, Hashimoto T, Matsumoto T, Kirii Y, Sawa M, Kinoshita T. A crucial role of Cys218 in configuring an unprecedented auto-inhibition form of MAP2K7. 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 doi:http://dx.doi.org/10.1016/j.bbrc.2016.03.036

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5b2k"

@@ Line 1: / Line 1: @@
 ==A crucial role of Cys218 in the stabilization of an unprecedented auto-inhibition form of MAP2K7==
-<StructureSection load='5b2k' size='340' side='right' caption='[[5b2k]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
+<StructureSection load='5b2k' size='340' side='right'caption='[[5b2k]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5b2k]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5b2k]] 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=5B2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B2K FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5b2m|5b2m]], [[5b2l|5b2l]]</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='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=5b2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2k OCA], [http://pdbe.org/5b2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b2k RCSB], [http://www.ebi.ac.uk/pdbsum/5b2k PDBsum]</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=5b2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b2k OCA], [http://pdbe.org/5b2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b2k RCSB], [http://www.ebi.ac.uk/pdbsum/5b2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b2k ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Mitogen-activated protein kinase kinase]]
 [[Category: Hashimoto, T]]

5b2k

From Proteopedia

Revision as of 10:01, 26 February 2020

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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