5arg
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==SMYD2 in complex with SGC probe BAY598== | |
| + | <StructureSection load='5arg' size='340' side='right' caption='[[5arg]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5arg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ARG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ARG FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H41:N-[1-(N-CYANO-N-[3-(DIFLUOROMETHOXY)PHENYL]CARBAMIMIDOYL)-3-(3,4-DICHLOROPHENYL)-4,5-DIHYDRO-1H-PYRAZOL-4-YL]-N-ETHYL-2-HYDROXYACETAMIDE'>H41</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5arg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5arg OCA], [http://pdbe.org/5arg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5arg RCSB], [http://www.ebi.ac.uk/pdbsum/5arg PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/SMYD2_HUMAN SMYD2_HUMAN]] Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB.<ref>PMID:17108971</ref> <ref>PMID:17805299</ref> <ref>PMID:18065756</ref> <ref>PMID:20870719</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Protein lysine methyltransferases have recently emerged as a new target class for the development of inhibitors that modulate gene transcription or signaling pathways. SET and MYND domain containing protein 2 (SMYD2) is a catalytic SET domain containing methyltransferase reported to monomethylate lysine residues on histone and nonhistone proteins. Although several studies have uncovered an important role of SMYD2 in promoting cancer by protein methylation, the biology of SMYD2 is far from being fully understood. Utilization of highly potent and selective chemical probes for target validation has emerged as a concept which circumvents possible limitations of knockdown experiments and, in particular, could result in an improved exploration of drug targets with a complex underlying biology. Here, we report the development of a potent, selective, and cell-active, substrate-competitive inhibitor of SMYD2, which is the first reported inhibitor suitable for in vivo target validation studies in rodents. | ||
| - | + | Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2.,Eggert E, Hillig RC, Koehr S, Stockigt D, Weiske J, Barak N, Mowat J, Brumby T, Christ CD, Ter Laak A, Lang T, Fernandez-Montalvan AE, Badock V, Weinmann H, Hartung IV, Barsyte-Lovejoy D, Szewczyk M, Kennedy S, Li F, Vedadi M, Brown PJ, Santhakumar V, Arrowsmith CH, Stellfeld T, Stresemann C J Med Chem. 2016 May 3. PMID:27075367<ref>PMID:27075367</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5arg" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Badock, V]] | ||
| + | [[Category: Barak, N]] | ||
| + | [[Category: Brumby, T]] | ||
| + | [[Category: Christ, C D]] | ||
[[Category: Eggert, E]] | [[Category: Eggert, E]] | ||
| + | [[Category: Fernandez-Montalvan, A E]] | ||
| + | [[Category: Hartung, I V]] | ||
| + | [[Category: Hillig, R C]] | ||
| + | [[Category: Koehr, S]] | ||
| + | [[Category: Laak, A ter]] | ||
| + | [[Category: Mowat, J]] | ||
| + | [[Category: Mueller, T]] | ||
[[Category: Stellfeld, T]] | [[Category: Stellfeld, T]] | ||
| - | [[Category: Barak, N]] | ||
[[Category: Stoeckigt, D]] | [[Category: Stoeckigt, D]] | ||
| - | [[Category: Mueller, T]] | ||
[[Category: Stresemann, C]] | [[Category: Stresemann, C]] | ||
| - | [[Category: Hartung, I.V]] | ||
[[Category: Weinmann, H]] | [[Category: Weinmann, H]] | ||
| - | [[Category: Ter Laak, A]] | ||
| - | [[Category: Brumby, T]] | ||
| - | [[Category: Koehr, S]] | ||
| - | [[Category: Christ, C.D]] | ||
[[Category: Weiske, J]] | [[Category: Weiske, J]] | ||
| - | [[Category: | + | [[Category: Drug target]] |
| - | [[Category: | + | [[Category: Methyltransferase]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| + | [[Category: Set domain]] | ||
| + | [[Category: Sgc probe]] | ||
| + | [[Category: Small molecule inhibitor]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 11:59, 13 May 2016
SMYD2 in complex with SGC probe BAY598
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Categories: Badock, V | Barak, N | Brumby, T | Christ, C D | Eggert, E | Fernandez-Montalvan, A E | Hartung, I V | Hillig, R C | Koehr, S | Laak, A ter | Mowat, J | Mueller, T | Stellfeld, T | Stoeckigt, D | Stresemann, C | Weinmann, H | Weiske, J | Drug target | Methyltransferase | Oxidoreductase | Set domain | Sgc probe | Small molecule inhibitor | Transferase
