5dtq
From Proteopedia
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==Crystal structure of Dot1L in complex with inhibitor CPD3 [(2,6-dichlorophenyl)(quinolin-6-yl)methanone]== | ==Crystal structure of Dot1L in complex with inhibitor CPD3 [(2,6-dichlorophenyl)(quinolin-6-yl)methanone]== | ||
| - | <StructureSection load='5dtq' size='340' side='right' caption='[[5dtq]], [[Resolution|resolution]] 2.61Å' scene=''> | + | <StructureSection load='5dtq' size='340' side='right'caption='[[5dtq]], [[Resolution|resolution]] 2.61Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5dtq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DTQ OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5dtq]] 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=5DTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DTQ FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.61Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5F6:(2,6-DICHLOROPHENYL)(QUINOLIN-6-YL)METHANONE'>5F6</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dtq OCA], [https://pdbe.org/5dtq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dtq RCSB], [https://www.ebi.ac.uk/pdbsum/5dtq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dtq ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == 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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5dtq" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Be | + | [[Category: Large Structures]] |
| - | [[Category: Moebitz | + | [[Category: Be C]] |
| - | [[Category: Scheufler | + | [[Category: Moebitz H]] |
| - | [[Category: Stauffer | + | [[Category: Scheufler C]] |
| - | + | [[Category: Stauffer F]] | |
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Current revision
Crystal structure of Dot1L in complex with inhibitor CPD3 [(2,6-dichlorophenyl)(quinolin-6-yl)methanone]
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