2ac5

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[[Image:2ac5.gif|left|200px]]
 
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{{Structure
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==Structure of human Mnk2 Kinase Domain mutant D228G==
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|PDB= 2ac5 |SIZE=350|CAPTION= <scene name='initialview01'>2ac5</scene>, resolution 3.2&Aring;
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<StructureSection load='2ac5' size='340' side='right'caption='[[2ac5]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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<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>
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|ACTIVITY= <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>
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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]] 3.2&#8491;</td></tr>
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|GENE=
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<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>
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|DOMAIN=
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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=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>
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|RELATEDENTRY=[[2ac3|2AC3]]
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</table>
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|RESOURCES=<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.ebi.ac.uk/pdbsum/2ac5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ac5 RCSB]</span>
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== Function ==
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}}
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ac/2ac5_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''Structure of human Mnk2 Kinase Domain mutant D228G'''
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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<ref>PMID:16216586</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2ac5" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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2AC5 is a [[Single protein]] structure of 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].
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Aicher B]]
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[[Category: Aicher, B.]]
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[[Category: Jackle H]]
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[[Category: Jackle, H.]]
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[[Category: Jakel S]]
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[[Category: Jakel, S.]]
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[[Category: Jauch R]]
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[[Category: Jauch, R.]]
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[[Category: Schreiter K]]
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[[Category: Schreiter, K.]]
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[[Category: Wahl MC]]
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[[Category: Wahl, M C.]]
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[[Category: dfg motif]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:50:40 2008''
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Current revision

Structure of human Mnk2 Kinase Domain mutant D228G

PDB ID 2ac5

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