6ylc
From Proteopedia
(Difference between revisions)
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==Biochemical, Cellular and Structural Characterization of Novel ERK3 Inhibitors== | ==Biochemical, Cellular and Structural Characterization of Novel ERK3 Inhibitors== | ||
| - | <StructureSection load='6ylc' size='340' side='right'caption='[[6ylc]]' scene=''> | + | <StructureSection load='6ylc' size='340' side='right'caption='[[6ylc]], [[Resolution|resolution]] 2.43Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YLC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YLC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ylc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YLC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YLC FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ylc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ylc OCA], [http://pdbe.org/6ylc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ylc RCSB], [http://www.ebi.ac.uk/pdbsum/6ylc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ylc ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OXW:5-fluoranyl-2-[5-[[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]amino]-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]benzenecarbonitrile'>OXW</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6yky|6yky]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK6, ERK3, PRKM6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ylc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ylc OCA], [http://pdbe.org/6ylc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ylc RCSB], [http://www.ebi.ac.uk/pdbsum/6ylc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ylc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MK06_HUMAN MK06_HUMAN]] Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Triazolo[4,5-d]pyrimidin-5-amines were identified from kinase selectivity screening as novel ERK3 inhibitors with sub-100 nanomolar potencies in a biochemical assay using MK5 as substrate and with an attractive kinase selectivity profile. ERK3 crystal structures clarified the inhibitor binding mode in the ATP pocket with impact on A-loop, GC-loop and alphaC-helix conformations suggesting a potential structural link towards MK5 interaction via the FHIEDE motif. The inhibitors also showed sub-100 nM potencies in a cellular ERK3 NanoBRET assay and with excellent correlation to the biochemical IC50s. This novel series provides valuable tool compounds to further investigate the biological function and activation mechanism of ERK3. | ||
| + | |||
| + | Biochemical, cellular and structural characterization of novel and selective ERK3 inhibitors.,Gradler U, Busch M, Leuthner B, Raba M, Burgdorf L, Lehmann M, Linde N, Esdar C Bioorg Med Chem Lett. 2020 Sep 11;30(22):127551. doi: 10.1016/j.bmcl.2020.127551. PMID:32927028<ref>PMID:32927028</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ylc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Graedler U]] | + | [[Category: Mitogen-activated protein kinase]] |
| + | [[Category: Graedler, U]] | ||
| + | [[Category: Erk3]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 07:50, 30 September 2020
Biochemical, Cellular and Structural Characterization of Novel ERK3 Inhibitors
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