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2ac5

From Proteopedia

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Current revision

Structure of human Mnk2 Kinase Domain mutant D228G

Structural highlights

2ac5 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MKNK2_HUMAN Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1 and Mnk2) target the translational machinery by phosphorylation of the eukaryotic initiation factor 4E (eIF4E). Here, we present the 2.1 A crystal structure of a nonphosphorylated Mnk2 fragment that encompasses the kinase domain. The results show Mnk-specific features such as a zinc binding motif and an atypical open conformation of the activation segment. In addition, the ATP binding pocket contains an Asp-Phe-Asp (DFD) in place of the canonical magnesium binding Asp-Phe-Gly (DFG) motif. The phenylalanine of this motif sticks into the ATP binding pocket and blocks ATP binding as observed with inhibitor bound and, thus, inactive p38 kinase. Replacement of the DFD by the canonical DFG motif affects the conformation of Mnk2, but not ATP binding and kinase activity. The results suggest that the ATP binding pocket and the activation segment of Mnk2 require conformational switches to provide kinase activity.

Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site.,Jauch R, Jakel S, Netter C, Schreiter K, Aicher B, Jackle H, Wahl MC Structure. 2005 Oct;13(10):1559-68. PMID:16216586^[10]

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

References

↑ Scheper GC, Morrice NA, Kleijn M, Proud CG. The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol. 2001 Feb;21(3):743-54. PMID:11154262 doi:10.1128/MCB.21.3.743-754.2001
↑ Knauf U, Tschopp C, Gram H. Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol Cell Biol. 2001 Aug;21(16):5500-11. PMID:11463832 doi:http://dx.doi.org/10.1128/MCB.21.16.5500-5511.2001
↑ Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG, Proud CG. The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization. Mol Cell Biol. 2003 Aug;23(16):5692-705. PMID:12897141
↑ Buxade M, Parra JL, Rousseau S, Shpiro N, Marquez R, Morrice N, Bain J, Espel E, Proud CG. The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNP A1. Immunity. 2005 Aug;23(2):177-89. PMID:16111636 doi:http://dx.doi.org/10.1016/j.immuni.2005.06.009
↑ Buxade M, Morrice N, Krebs DL, Proud CG. The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha. J Biol Chem. 2008 Jan 4;283(1):57-65. Epub 2007 Oct 26. PMID:17965020 doi:http://dx.doi.org/10.1074/jbc.M705286200
↑ Dolniak B, Katsoulidis E, Carayol N, Altman JK, Redig AJ, Tallman MS, Ueda T, Watanabe-Fukunaga R, Fukunaga R, Platanias LC. Regulation of arsenic trioxide-induced cellular responses by Mnk1 and Mnk2. J Biol Chem. 2008 May 2;283(18):12034-42. doi: 10.1074/jbc.M708816200. Epub 2008 , Feb 25. PMID:18299328 doi:http://dx.doi.org/10.1074/jbc.M708816200
↑ Shveygert M, Kaiser C, Bradrick SS, Gromeier M. Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by mitogen-activated protein kinase occurs through modulation of Mnk1-eIF4G interaction. Mol Cell Biol. 2010 Nov;30(21):5160-7. doi: 10.1128/MCB.00448-10. Epub 2010 Sep, 7. PMID:20823271 doi:http://dx.doi.org/10.1128/MCB.00448-10
↑ Li Y, Yue P, Deng X, Ueda T, Fukunaga R, Khuri FR, Sun SY. Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E. Neoplasia. 2010 Oct;12(10):848-55. PMID:20927323
↑ Joshi S, Sharma B, Kaur S, Majchrzak B, Ueda T, Fukunaga R, Verma AK, Fish EN, Platanias LC. Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis. J Biol Chem. 2011 Feb 25;286(8):6017-26. doi: 10.1074/jbc.M110.197921. Epub 2010 , Dec 13. PMID:21149447 doi:http://dx.doi.org/10.1074/jbc.M110.197921
↑ Jauch R, Jakel S, Netter C, Schreiter K, Aicher B, Jackle H, Wahl MC. Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site. Structure. 2005 Oct;13(10):1559-68. PMID:16216586 doi:10.1016/j.str.2005.07.013

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ac5"

@@ Line 1: / Line 1: @@
 ==Structure of human Mnk2 Kinase Domain mutant D228G==
-<StructureSection load='2ac5' size='340' side='right' caption='[[2ac5]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='2ac5' size='340' side='right'caption='[[2ac5]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ac5]] is a 1 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=2AC5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AC5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ac5]] 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=2AC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AC5 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ac3|2ac3]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=2ac5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ac5 OCA], [https://pdbe.org/2ac5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ac5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ac5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ac5 ProSAT]</span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ac5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ac5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ac5 RCSB], [http://www.ebi.ac.uk/pdbsum/2ac5 PDBsum]</span></td></tr>
+</table>
-<table>
+== Function ==
+[https://www.uniprot.org/uniprot/MKNK2_HUMAN MKNK2_HUMAN] Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.<ref>PMID:11154262</ref> <ref>PMID:11463832</ref> <ref>PMID:12897141</ref> <ref>PMID:16111636</ref> <ref>PMID:17965020</ref> <ref>PMID:18299328</ref> <ref>PMID:20823271</ref> <ref>PMID:20927323</ref> <ref>PMID:21149447</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ac/2ac5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ac/2ac5_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ac5 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2ac5" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
@@ Line 34: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Aicher, B.]]
+[[Category: Aicher B]]
-[[Category: Jackle, H.]]
+[[Category: Jackle H]]
-[[Category: Jakel, S.]]
+[[Category: Jakel S]]
-[[Category: Jauch, R.]]
+[[Category: Jauch R]]
-[[Category: Schreiter, K.]]
+[[Category: Schreiter K]]
-[[Category: Wahl, M C.]]
+[[Category: Wahl MC]]
-[[Category: Dfg motif]]
-[[Category: Transferase]]

2ac5

From Proteopedia

Current revision

Structure of human Mnk2 Kinase Domain mutant D228G

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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