6t1j
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6t1j is ON HOLD Authors: Chaikuad, A., Heidenreich, D., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Fedorov, O., Knapp, S., Structural Genomics Co...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of MLLT1 (ENL) YEATS domain in complexed with piperazine-urea derivative 2== | |
| + | <StructureSection load='6t1j' size='340' side='right'caption='[[6t1j]], [[Resolution|resolution]] 1.97Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6t1j]] 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=6T1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T1J 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]] 1.97Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M7T:~{N}-[[4-(pyrrolidin-1-ylmethyl)phenyl]methyl]-4-thiophen-2-ylcarbonyl-piperazine-1-carboxamide'>M7T</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=6t1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t1j OCA], [https://pdbe.org/6t1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t1j RCSB], [https://www.ebi.ac.uk/pdbsum/6t1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t1j ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN] A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with KMT2A/MLL1. The result is a rogue activator protein. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | YEATS-domain-containing MLLT1 is an acetyl/acyl-lysine reader domain, which is structurally distinct from well-studied bromodomains and has been strongly associated in development of cancer. Here, we characterized piperazine-urea derivatives as an acetyl/acyl-lysine mimetic moiety for MLLT1. Crystal structures revealed distinct interaction mechanisms of this chemotype compared to the recently described benzimidazole-amide based inhibitors, exploiting different binding pockets within the protein. Thus, the piperazine-urea scaffold offers an alternative strategy for targeting the YEATS domain family. | ||
| - | + | Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1.,Ni X, Heidenreich D, Christott T, Bennett J, Moustakim M, Brennan PE, Fedorov O, Knapp S, Chaikuad A ACS Med Chem Lett. 2019 Nov 25;10(12):1661-1666. doi:, 10.1021/acsmedchemlett.9b00460. eCollection 2019 Dec 12. PMID:31857843<ref>PMID:31857843</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6t1j" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: Fedorov | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Arrowsmith CH]] |
| + | [[Category: Bountra C]] | ||
| + | [[Category: Chaikuad A]] | ||
| + | [[Category: Edwards AM]] | ||
| + | [[Category: Fedorov O]] | ||
| + | [[Category: Heidenreich D]] | ||
| + | [[Category: Knapp S]] | ||
Current revision
Crystal structure of MLLT1 (ENL) YEATS domain in complexed with piperazine-urea derivative 2
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