3fyk

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{{Seed}}
 
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[[Image:3fyk.jpg|left|200px]]
 
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==Crystal structure of a benzthiophene lead bound to MAPKAP Kinase-2 (MK-2)==
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The line below this paragraph, containing "STRUCTURE_3fyk", creates the "Structure Box" on the page.
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<StructureSection load='3fyk' size='340' side='right'caption='[[3fyk]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3fyk]] 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=3FYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FYK FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 3.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B98:(3R)-3-(AMINOMETHYL)-9-METHOXY-1,2,3,4-TETRAHYDRO-5H-[1]BENZOTHIENO[3,2-E][1,4]DIAZEPIN-5-ONE'>B98</scene></td></tr>
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{{STRUCTURE_3fyk| PDB=3fyk | SCENE= }}
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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=3fyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fyk OCA], [https://pdbe.org/3fyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fyk RCSB], [https://www.ebi.ac.uk/pdbsum/3fyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fyk ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MAPK2_HUMAN MAPK2_HUMAN] Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.<ref>PMID:8280084</ref> <ref>PMID:8093612</ref> <ref>PMID:8774846</ref> <ref>PMID:10383393</ref> <ref>PMID:12456657</ref> <ref>PMID:11844797</ref> <ref>PMID:12565831</ref> <ref>PMID:14499342</ref> <ref>PMID:14517288</ref> <ref>PMID:15014438</ref> <ref>PMID:15629715</ref> <ref>PMID:16456544</ref> <ref>PMID:16278218</ref> <ref>PMID:17481585</ref> <ref>PMID:18021073</ref> <ref>PMID:20932473</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/fy/3fyk_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=3fyk 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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Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.
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===Crystal structure of a benzthiophene lead bound to MAPKAP Kinase-2 (MK-2)===
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Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency.,Anderson DR, Meyers MJ, Kurumbail RG, Caspers N, Poda GI, Long SA, Pierce BS, Mahoney MW, Mourey RJ, Parikh MD Bioorg Med Chem Lett. 2009 Aug 15;19(16):4882-4. Epub 2009 Feb 8. PMID:19616942<ref>PMID:19616942</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 3fyk" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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3FYK is a 1 chain 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=3FYK OCA].
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*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated 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: Caspers, N.]]
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[[Category: Caspers N]]
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[[Category: Kurumbail, R G.]]
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[[Category: Kurumbail RG]]
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[[Category: Alternative splicing]]
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[[Category: Atp-binding]]
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[[Category: Kinase]]
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[[Category: Map kinase]]
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[[Category: Mapkap-2]]
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[[Category: Mk-2]]
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[[Category: Mk2]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Ser/thr kinase]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 9 12:30:30 2009''
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Current revision

Crystal structure of a benzthiophene lead bound to MAPKAP Kinase-2 (MK-2)

PDB ID 3fyk

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