5dtr
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5dtr is ON HOLD until Paper Publication Authors: Scheufler, C., Be, C., Moebitz, H., Stauffer, F. Description: Category: Unreleased Structures...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Dot1L in complex with inhibitor CPD5 [N-(2,6-dichlorophenyl)-4-methoxy-N-methylquinolin-6-amine]== | |
| + | <StructureSection load='5dtr' size='340' side='right'caption='[[5dtr]], [[Resolution|resolution]] 2.34Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5dtr]] is a 2 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=5DTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DTR 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]] 2.34Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5F7:N-(2,6-DICHLOROPHENYL)-4-METHOXY-N-METHYLQUINOLIN-6-AMINE'>5F7</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=5dtr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dtr OCA], [https://pdbe.org/5dtr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dtr RCSB], [https://www.ebi.ac.uk/pdbsum/5dtr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dtr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mixed lineage leukemia (MLL) gene rearrangement induces leukemic transformation by ectopic recruitment of disruptor of telomeric silencing 1-like protein (DOT1L), a lysine histone methyltransferase, leading to local hypermethylation of H3K79 and misexpression of genes (including HoxA), which drive the leukemic phenotype. A weak fragment-based screening hit identified by SPR was cocrystallized with DOT1L and optimized using structure-based ligand optimization to yield compound 8 (IC50 = 14 nM). This series of inhibitors is structurally not related to cofactor SAM and is not interacting within the SAM binding pocket but induces a pocket adjacent to the SAM binding site. | ||
| - | + | Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket.,Scheufler C, Mobitz H, Gaul C, Ragot C, Be C, Fernandez C, Beyer KS, Tiedt R, Stauffer F ACS Med Chem Lett. 2016 Jun 6;7(8):730-4. doi: 10.1021/acsmedchemlett.6b00168., eCollection 2016 Aug 11. PMID:27563394<ref>PMID:27563394</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5dtr" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Moebitz | + | ==See Also== |
| - | [[Category: Stauffer | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Be C]] | ||
| + | [[Category: Moebitz H]] | ||
| + | [[Category: Scheufler C]] | ||
| + | [[Category: Stauffer F]] | ||
Current revision
Crystal structure of Dot1L in complex with inhibitor CPD5 [N-(2,6-dichlorophenyl)-4-methoxy-N-methylquinolin-6-amine]
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