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{{STRUCTURE_3m42|  PDB=3m42  |  SCENE=  }}
==Crystal structure of MAPKAP kinase 2 (MK2) complexed with a tetracyclic ATP site inhibitor==
===Crystal structure of MAPKAP kinase 2 (MK2) complexed with a tetracyclic ATP site inhibitor===
<StructureSection load='3m42' size='340' side='right' caption='[[3m42]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
 
== Structural highlights ==
==Function==
<table><tr><td colspan='2'>[[3m42]] 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=3M42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M42 FirstGlance]. <br>
[[http://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>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HGF:2-[5-(2-METHOXYETHOXY)PYRIDIN-3-YL]-8,9,10,11-TETRAHYDRO-7H-PYRIDO[3,4 4,5]PYRROLO[2,3-F]ISOQUINOLIN-7-ONE'>HGF</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">[[3kga|3kga]], [[3m2w|3m2w]]</td></tr>
==About this Structure==
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPKAPK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
[[3m42]] 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=3M42 OCA].  
<tr id='activity'><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3m42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m42 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m42 RCSB], [http://www.ebi.ac.uk/pdbsum/3m42 PDBsum]</span></td></tr>
==Reference==
</table>
<references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Be, C.]]
[[Category: Be, C]]
[[Category: Huppertz, C.]]
[[Category: Huppertz, C]]
[[Category: Izaac, A.]]
[[Category: Izaac, A]]
[[Category: Kroemer, M.]]
[[Category: Kroemer, M]]
[[Category: Revesz, L.]]
[[Category: Revesz, L]]
[[Category: Scheufler, C.]]
[[Category: Scheufler, C]]
[[Category: Schlapbach, A.]]
[[Category: Schlapbach, A]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Atp-site kinase inhibitor]]
[[Category: Atp-site kinase inhibitor]]

Revision as of 15:58, 18 December 2014

Crystal structure of MAPKAP kinase 2 (MK2) complexed with a tetracyclic ATP site inhibitor

3m42, resolution 2.68Å

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