5dtm
From Proteopedia
(Difference between revisions)
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5F4:4-(2,6-DICHLOROBENZOYL)-N-METHYL-1H-PYRROLE-2-CARBOXAMIDE'>5F4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5F4:4-(2,6-DICHLOROBENZOYL)-N-METHYL-1H-PYRROLE-2-CARBOXAMIDE'>5F4</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></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=5dtm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dtm OCA], [http://pdbe.org/5dtm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dtm RCSB], [http://www.ebi.ac.uk/pdbsum/5dtm PDBsum]</span></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=5dtm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dtm OCA], [http://pdbe.org/5dtm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dtm RCSB], [http://www.ebi.ac.uk/pdbsum/5dtm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dtm ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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. | [[http://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 5dtm" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 04:39, 9 September 2016
Crystal structure of Dot1L in complex with inhibitor CPD1 [4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide]
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