6t1m: Difference between revisions
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<StructureSection load='6t1m' size='340' side='right'caption='[[6t1m]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='6t1m' size='340' side='right'caption='[[6t1m]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6t1m]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6t1m]] 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=6T1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T1M FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M8K:4-cyano-~{N}-[2-(piperidin-1-ylmethyl)-1~{H}-benzimidazol-5-yl]benzamide'>M8K</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</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=M8K:4-cyano-~{N}-[2-(piperidin-1-ylmethyl)-1~{H}-benzimidazol-5-yl]benzamide'>M8K</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=6t1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t1m OCA], [https://pdbe.org/6t1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t1m RCSB], [https://www.ebi.ac.uk/pdbsum/6t1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t1m ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 25: | Line 25: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: Bountra | [[Category: Bountra C]] | ||
[[Category: Brennan | [[Category: Brennan PE]] | ||
[[Category: Chaikuad | [[Category: Chaikuad A]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Fedorov | [[Category: Fedorov O]] | ||
[[Category: Heidenreich | [[Category: Heidenreich D]] | ||
[[Category: Knapp | [[Category: Knapp S]] | ||
[[Category: Moustakim | [[Category: Moustakim M]] | ||
Latest revision as of 15:52, 24 January 2024
Crystal structure of MLLT1 (ENL) YEATS domain in complexed with benzimidazole-amide derivative 4Crystal structure of MLLT1 (ENL) YEATS domain in complexed with benzimidazole-amide derivative 4
Structural highlights
DiseaseENL_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. FunctionENL_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.[1] [2] Publication Abstract from PubMedYEATS-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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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