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6ib2

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Revision as of 07:06, 27 March 2019

The structure of MKK7 in complex with the covalent 4-amino-pyrazolopyrimidine 4a

Structural highlights

6ib2 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.
Ligands:
Related:	6ib0
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

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^[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
↑ Wolle P, Hardick J, Cronin SJF, Engel J, Baumann M, Lategahn J, Penninger JM, Rauh D. Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors. J Med Chem. 2019 Feb 21. doi: 10.1021/acs.jmedchem.9b00102. PMID:30768270 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00102

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/6ib2"

@@ Line 1: / Line 1: @@
 ==The structure of MKK7 in complex with the covalent 4-amino-pyrazolopyrimidine 4a==
-<StructureSection load='6ib2' size='340' side='right' caption='[[6ib2]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='6ib2' size='340' side='right'caption='[[6ib2]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ib2]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IB2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ib2]] 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=6IB2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IB2 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ib0|6ib0]]</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=6ib2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ib2 OCA], [http://pdbe.org/6ib2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ib2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ib2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ib2 ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Mitogen-activated protein kinase kinase]]
 [[Category: Hardick, J]]

6ib2

From Proteopedia

Revision as of 07:06, 27 March 2019

The structure of MKK7 in complex with the covalent 4-amino-pyrazolopyrimidine 4a

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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