View source for 8pj7


==MLLT3 in complex with compound PFI-6==
<StructureSection load='8pj7' size='340' side='right'caption='[[8pj7]], [[Resolution|resolution]] 1.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8pj7]] 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=8PJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PJ7 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]] 1.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZJ9:~{N}-[(1~{R})-2,3-dihydro-1~{H}-inden-1-yl]-5-[4-(dimethylcarbamoyl)-3-oxidanyl-phenyl]-1,2-oxazole-3-carboxamide'>ZJ9</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=8pj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pj7 OCA], [https://pdbe.org/8pj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pj7 RCSB], [https://www.ebi.ac.uk/pdbsum/8pj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pj7 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AF9_HUMAN AF9_HUMAN] A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein.
== Function ==
[https://www.uniprot.org/uniprot/AF9_HUMAN AF9_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 ==
Epigenetic proteins containing YEATS domains (YD) are an emerging target class in drug discovery. Described herein are the discovery and characterization efforts associated with PFI-6, a new chemical probe for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). For hit identification, fragment-like mimetics of endogenous YD ligands (crotonylated histone-containing proteins), were synthesized via parallel medicinal chemistry (PMC) and screened for MLLT1 binding. Subsequent SAR studies led to iterative MLLT1/3 binding and selectivity improvements, culminating in the discovery of PFI-6. PFI-6 demonstrates good affinity and selectivity for MLLT1/3 vs. other human YD proteins (YEATS2/4) and engages MLLT3 in cells. Small-molecule X-ray co-crystal structures of two molecules, including PFI-6, bound to the YD of MLLT1/3 are also described. PFI-6 may be a useful tool molecule to better understand the biological effects associated with modulation of MLLT1/3.

Discovery of PFI-6, a small-molecule chemical probe for the YEATS domain of MLLT1 and MLLT3.,Raux B, Buchan KA, Bennett J, Christott T, Dowling MS, Farnie G, Fedorov O, Gamble V, Gileadi C, Giroud C, Huber KVM, Korczynska M, Limberakis C, Narayanan A, Owen DR, Saez LD, Stock IA, Londregan AT Bioorg Med Chem Lett. 2023 Nov 7:129546. doi: 10.1016/j.bmcl.2023.129546. PMID:37944866<ref>PMID:37944866</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8pj7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith C]]
[[Category: Bountra C]]
[[Category: Diaz-Saez L]]
[[Category: Edwards A]]
[[Category: Fedorov O]]
[[Category: Huber KVM]]
[[Category: Londregan AT]]
[[Category: Owen DR]]
[[Category: Raux B]]