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3aln

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Revision as of 18:50, 4 August 2016

Crystal Structure of human non-phosphorylated MKK4 kinase domain complexed with AMP-PNP

Structural highlights

3aln is a 3 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:	3alo
Gene:	JNKK1, MAP2K4, MEK4, MKK4, PRKMK4, SERK1 (HUMAN)
Activity:	Mitogen-activated protein kinase kinase, with EC number 2.7.12.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MP2K4_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 MAP2K7/MKK7, 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 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.^[1]

Publication Abstract from PubMed

MKK4 activates both JNKs and p38s. We determined the crystal structures of human non-phosphorylated MKK4 kinase domain (npMKK4) complexed with AMP-PNP (npMKK4/AMP) and a ternary complex of npMKK4, AMP-PNP and p38alpha peptide (npMKK4/AMP/p38). These crystal structures revealed that the p38alpha peptide-bound npMKK4 at the allosteric site rather than at the putative substrate binding site and induced an auto-inhibition state. While the activation loop of the npMKK4/AMP complex was disordered, in the npMKK4/AMP/p38 complex it configured a long alpha-helix, which prevented substrate access to the active site and alphaC-helix movement to the active configuration of MKK4.

Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state.,Matsumoto T, Kinoshita T, Kirii Y, Yokota K, Hamada K, Tada T Biochem Biophys Res Commun. 2010 Sep 24;400(3):369-73. Epub 2010 Aug 21. PMID:20732303^[2]

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

References

↑ Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286-90. PMID:7716521
↑ Matsumoto T, Kinoshita T, Kirii Y, Yokota K, Hamada K, Tada T. Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state. Biochem Biophys Res Commun. 2010 Sep 24;400(3):369-73. Epub 2010 Aug 21. PMID:20732303 doi:10.1016/j.bbrc.2010.08.071

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3aln"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of human non-phosphorylated MKK4 kinase domain complexed with AMP-PNP==
 <StructureSection load='3aln' size='340' side='right' caption='[[3aln]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3aln]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ALN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ALN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3aln]] is a 3 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=3ALN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ALN FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3alo|3alo]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JNKK1, MAP2K4, MEK4, MKK4, PRKMK4, SERK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">JNKK1, MAP2K4, MEK4, MKK4, PRKMK4, SERK1 ([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=3aln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aln OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3aln RCSB], [http://www.ebi.ac.uk/pdbsum/3aln 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=3aln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aln OCA], [http://pdbe.org/3aln PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3aln RCSB], [http://www.ebi.ac.uk/pdbsum/3aln PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3aln ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3aln" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Mitogen-activated protein kinase kinase]]
 [[Category: Hamada, K]]

3aln

From Proteopedia

Revision as of 18:50, 4 August 2016

Crystal Structure of human non-phosphorylated MKK4 kinase domain complexed with AMP-PNP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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