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2hw6

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[[Image:2hw6.gif|left|200px]]
 
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{{Structure
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==Crystal structure of Mnk1 catalytic domain==
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|PDB= 2hw6 |SIZE=350|CAPTION= <scene name='initialview01'>2hw6</scene>, resolution 2.50&Aring;
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<StructureSection load='2hw6' size='340' side='right'caption='[[2hw6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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<table><tr><td colspan='2'>[[2hw6]] is a 2 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=2HW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HW6 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]] 2.5&#8491;</td></tr>
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|GENE= MKNK1, MNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2hw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hw6 OCA], [https://pdbe.org/2hw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hw6 RCSB], [https://www.ebi.ac.uk/pdbsum/2hw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hw6 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[2ac3|2AC3]], [[2ac5|2AC5]], [[2hw7|2HW7]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hw6 OCA], [http://www.ebi.ac.uk/pdbsum/2hw6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hw6 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/MKNK1_HUMAN MKNK1_HUMAN] 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.<ref>PMID:9155018</ref> <ref>PMID:11463832</ref> <ref>PMID:15350534</ref> <ref>PMID:9878069</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/hw/2hw6_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=2hw6 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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Autoinhibition is a recurring mode of protein kinase regulation and can be based on diverse molecular mechanisms. Here, we show by crystal structure analysis, nuclear magnetic resonance (NMR)-based nucleotide affinity studies and rational mutagenesis that nonphosphorylated mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1 is autoinhibited by conversion of the activation segment into an autoinhibitory module. In a Mnk1 crystal structure, the activation segment is repositioned via a Mnk-specific sequence insertion at the N-terminal lobe with the following consequences: (i) the peptide substrate binding site is deconstructed, (ii) the interlobal cleft is narrowed, (iii) an essential Lys-Glu pair is disrupted and (iv) the magnesium-binding loop is locked into an ATP-competitive conformation. Consistently, deletion of the Mnk-specific insertion or removal of a conserved phenylalanine side chain, which induces a blockade of the ATP pocket, increase the ATP affinity of Mnk1. Structural rearrangements required for the activation of Mnks are apparent from the cocrystal structure of a Mnk2 D228G -staurosporine complex and can be modeled on the basis of crystal packing interactions. Our data suggest a novel regulatory mechanism specific for the Mnk subfamily.
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'''Crystal structure of Mnk1 catalytic domain'''
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Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.,Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. PMID:16917500<ref>PMID:16917500</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 2hw6" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Autoinhibition is a recurring mode of protein kinase regulation and can be based on diverse molecular mechanisms. Here, we show by crystal structure analysis, nuclear magnetic resonance (NMR)-based nucleotide affinity studies and rational mutagenesis that nonphosphorylated mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1 is autoinhibited by conversion of the activation segment into an autoinhibitory module. In a Mnk1 crystal structure, the activation segment is repositioned via a Mnk-specific sequence insertion at the N-terminal lobe with the following consequences: (i) the peptide substrate binding site is deconstructed, (ii) the interlobal cleft is narrowed, (iii) an essential Lys-Glu pair is disrupted and (iv) the magnesium-binding loop is locked into an ATP-competitive conformation. Consistently, deletion of the Mnk-specific insertion or removal of a conserved phenylalanine side chain, which induces a blockade of the ATP pocket, increase the ATP affinity of Mnk1. Structural rearrangements required for the activation of Mnks are apparent from the cocrystal structure of a Mnk2 D228G -staurosporine complex and can be modeled on the basis of crystal packing interactions. Our data suggest a novel regulatory mechanism specific for the Mnk subfamily.
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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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==About this Structure==
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<references/>
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2HW6 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=2HW6 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment., Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC, EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16917500 16917500]
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[[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: Jauch R]]
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[[Category: Jauch, R.]]
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[[Category: Wahl MC]]
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[[Category: Wahl, M C.]]
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[[Category: drug design]]
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[[Category: mnk1]]
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[[Category: phosphorylation]]
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[[Category: protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:36:16 2008''
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Current revision

Crystal structure of Mnk1 catalytic domain

PDB ID 2hw6

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