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==Crystal structure of MLLT1 YEATS domain T1 mutant in complex with benzimidazole-amide based compound 1==
==Crystal structure of MLLT1 YEATS domain T1 mutant in complex with benzimidazole-amide based compound 1==
<StructureSection load='7b10' size='340' side='right'caption='[[7b10]]' scene=''>
<StructureSection load='7b10' size='340' side='right'caption='[[7b10]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B10 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7b10]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B10 FirstGlance]. <br>
</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=7b10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b10 OCA], [https://pdbe.org/7b10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b10 RCSB], [https://www.ebi.ac.uk/pdbsum/7b10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b10 ProSAT]</span></td></tr>
</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=GKT:3-iodanyl-4-methyl-~{N}-[2-(piperidin-1-ylmethyl)-3~{H}-benzimidazol-5-yl]benzamide'>GKT</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MLLT1, ENL, LTG19, YEATS1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7b10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b10 OCA], [https://pdbe.org/7b10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b10 RCSB], [https://www.ebi.ac.uk/pdbsum/7b10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b10 ProSAT]</span></td></tr>
</table>
</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 ==
Dysfunction of YEATS-domain-containing MLLT1, an acetyl/acyl-lysine dependent epigenetic reader domain, has been implicated in the development of aggressive cancers. Mutations in the YEATS domain have been recently reported as a cause of MLLT1 aberrant reader function. However, the structural basis for the reported alterations in affinity for acetylated/acylated histone has remained elusive. Here, we report the crystal structures of both insertion and substitution mutants present in cancer, revealing significant conformational changes of the YEATS-domain loop 8. Structural comparison demonstrates that not only did such alteration alter the binding interface for acetylated/acylated histones, but the sequence alterations in the loop in T1 mutant may enable dimeric assembly consistent with inducing self-association behavior. Nevertheless, we show that also the MLLT1 mutants can be targeted by developed acetyllysine mimetic inhibitors with affinities similarly to wild-type. Our report provides a structural basis for the altered behaviors and a potential strategy for targeting oncogenic MLLT1 mutants.
Structure and Inhibitor Binding Characterization of Oncogenic MLLT1 Mutants.,Ni X, Londregan AT, Owen DR, Knapp S, Chaikuad A ACS Chem Biol. 2021 Mar 21. doi: 10.1021/acschembio.0c00960. PMID:33749253<ref>PMID:33749253</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7b10" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Brennan PE]]
[[Category: Brennan, P E]]
[[Category: Chaikuad A]]
[[Category: Chaikuad, A]]
[[Category: Knapp S]]
[[Category: Knapp, S]]
[[Category: Ni X]]
[[Category: Ni, X]]
[[Category: Structural genomic]]
[[Category: Sgc]]
[[Category: T1 mutant]]
[[Category: Transcription]]
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