6yll: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 ==Biochemical, Cellular and Structural Characterization of Novel ERK3 Inhibitors==
-<StructureSection load='6yll' size='340' side='right'caption='[[6yll]]' scene=''>
+<StructureSection load='6yll' size='340' side='right'caption='[[6yll]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YLL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YLL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6yll]] is a 2 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=6YLL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YLL 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=6yll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yll OCA], [http://pdbe.org/6yll PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yll RCSB], [http://www.ebi.ac.uk/pdbsum/6yll PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yll 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=OYB:~{N}4-[3-(4-methoxyphenyl)-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl]cyclohexane-1,4-diamine'>OYB</scene></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=6yll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yll OCA], [http://pdbe.org/6yll PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yll RCSB], [http://www.ebi.ac.uk/pdbsum/6yll PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yll ProSAT]</span></td></tr>
 </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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6yll" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Graedler U]]
+[[Category: Mitogen-activated protein kinase]]
+[[Category: Graedler, U]]
+[[Category: Erk3]]
+[[Category: Inhibitor]]
+[[Category: Transferase]]