6jlr
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of wild type MNK2 in complex with inhibitor== | |
| + | <StructureSection load='6jlr' size='340' side='right'caption='[[6jlr]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6jlr]] 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=6JLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JLR FirstGlance]. <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]] 2.901Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BV9:4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]benzamide'>BV9</scene></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=6jlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jlr OCA], [https://pdbe.org/6jlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jlr RCSB], [https://www.ebi.ac.uk/pdbsum/6jlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jlr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MKNK2_HUMAN MKNK2_HUMAN] Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.<ref>PMID:11154262</ref> <ref>PMID:11463832</ref> <ref>PMID:12897141</ref> <ref>PMID:16111636</ref> <ref>PMID:17965020</ref> <ref>PMID:18299328</ref> <ref>PMID:20823271</ref> <ref>PMID:20927323</ref> <ref>PMID:21149447</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dysregulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers. Mitogen-activated protein kinase (MAPK) interacting kinases 1 and 2 (MNK1 and MNK2) play a fundamental role in activation of eIF4E. Structure-activity relationship-driven expansion of a fragment hit led to discovery of dual MNK1 and MNK2 inhibitors based on a novel pyridine-benzamide scaffold. The compounds possess promising in vitro and in vivo pharmacokinetic profiles and show potent on target inhibition of eIF4E phosphorylation in cells. | ||
| - | + | Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.,Kwiatkowski J, Liu B, Pang S, Ahmad NHB, Wang G, Poulsen A, Yang H, Poh YR, Tee DHY, Ong E, Retna P, Dinie N, Kwek P, Wee JLK, Manoharan V, Low CB, Seah PG, Pendharkar V, Sangthongpitag K, Joy J, Baburajendran N, Jansson AE, Nacro K, Hill J, Keller TH, Hung AW J Med Chem. 2020 Jan 23;63(2):621-637. doi: 10.1021/acs.jmedchem.9b01582. Epub, 2020 Jan 7. PMID:31910010<ref>PMID:31910010</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6jlr" style="background-color:#fffaf0;"></div> |
| - | [[Category: Baburajendran | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Baburajendran N]] | ||
| + | [[Category: Hill J]] | ||
Current revision
Crystal structure of wild type MNK2 in complex with inhibitor
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