4jg6
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4jg6 is ON HOLD Authors: Miller, R. M., Paavilainen, V. O., Krishnan, S., Serafimova, I. M., Taunton, J. Description: RSK2 CTD bound to 2-cyano-3-(...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==RSK2 CTD bound to 2-cyano-3-(1H-indazol-5-yl)acrylamide== | |
| + | <StructureSection load='4jg6' size='340' side='right'caption='[[4jg6]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4jg6]] 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=4JG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JG6 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]] 2.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1LB:(2S)-2-CYANO-3-(1H-INDAZOL-5-YL)PROPANAMIDE'>1LB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4jg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jg6 OCA], [https://pdbe.org/4jg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jg6 RCSB], [https://www.ebi.ac.uk/pdbsum/4jg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jg6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fragment-based ligand design and covalent targeting of noncatalytic cysteines have been employed to develop potent and selective kinase inhibitors. Here, we combine these approaches, starting with a panel of low-molecular-weight, heteroaryl-susbstituted cyanoacrylamides, which we have previously shown to form reversible covalent bonds with cysteine thiols. Using this strategy, we identify electrophilic fragments with sufficient ligand efficiency and selectivity to serve as starting points for the first reported inhibitors of the MSK1 C-terminal kinase domain. Guided by X-ray co-crystal structures, indazole fragment 1 was elaborated to afford 12 (RMM-46), a reversible covalent inhibitor that exhibits high ligand efficiency and selectivity for MSK/RSK-family kinases. At nanomolar concentrations, 12 blocked activation of cellular MSK and RSK, as well as downstream phosphorylation of the critical transcription factor, CREB. | ||
| - | + | Electrophilic fragment-based design of reversible covalent kinase inhibitors.,Miller RM, Paavilainen VO, Krishnan S, Serafimova IM, Taunton J J Am Chem Soc. 2013 Apr 10;135(14):5298-301. doi: 10.1021/ja401221b. Epub 2013, Mar 29. PMID:23540679<ref>PMID:23540679</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4jg6" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ribosomal protein S6 kinase 3D structures|Ribosomal protein S6 kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Krishnan S]] | ||
| + | [[Category: Miller RM]] | ||
| + | [[Category: Paavilainen VO]] | ||
| + | [[Category: Serafimova IM]] | ||
| + | [[Category: Taunton J]] | ||
Current revision
RSK2 CTD bound to 2-cyano-3-(1H-indazol-5-yl)acrylamide
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