3r2b: Difference between revisions

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 ==MK2 kinase bound to Compound 5b==
-<StructureSection load='3r2b' size='340' side='right' caption='[[3r2b]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='3r2b' size='340' side='right'caption='[[3r2b]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3r2b]] is a 12 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=3R2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R2B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3r2b]] is a 12 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=3R2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R2B FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=05B:2-[2-(1,3-BENZODIOXOL-5-YL)PYRIMIDIN-4-YL]-5,6-DIHYDROSPIRO[PIPERIDINE-4,7-PYRROLO[3,2-C]PYRIDIN]-4(1H)-ONE'>05B</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]] 2.9&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r1n|3r1n]], [[3r2y|3r2y]], [[3r30|3r30]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=05B:2-[2-(1,3-BENZODIOXOL-5-YL)PYRIMIDIN-4-YL]-5,6-DIHYDROSPIRO[PIPERIDINE-4,7-PYRROLO[3,2-C]PYRIDIN]-4(1H)-ONE'>05B</scene></td></tr>
-<tr><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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r2b OCA], [https://pdbe.org/3r2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r2b RCSB], [https://www.ebi.ac.uk/pdbsum/3r2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r2b ProSAT]</span></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>
+</table>
-<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=3r2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r2b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r2b RCSB], [http://www.ebi.ac.uk/pdbsum/3r2b PDBsum]</span></td></tr>
+== Function ==
-<table>
+[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>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model.
-Structure-based lead identification of ATP-competitive MK2 inhibitors.,Barf T, Kaptein A, Wilde SD, Heijden RV, Someren RV, Demont D, Schultz-Fademrecht C, Versteegh J, Zeeland MV, Seegers N, Kazemier B, Kar BV, Hoek MV, Roos JD, Klop H, Smeets R, Hofstra C, Hornberg J, Oubrie A Bioorg Med Chem Lett. 2011 Apr 16. PMID:21565500<ref>PMID:21565500</ref>
-From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+==See Also==
-</div>
+*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
 == References ==
 <references/>
@@ Line 22: / Line 18: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Oubrie, A.]]
+[[Category: Oubrie A]]
-[[Category: Versteegh, J.]]
+[[Category: Versteegh J]]
-[[Category: Zeeland, M van.]]
+[[Category: Van Zeeland M]]
-[[Category: Kinase domain]]
-[[Category: Kinase domain with bound inhibitor]]
-[[Category: Phosphotransferase]]
-[[Category: Transferase-transferase inhibitor complex]]