View source for 6yuh


==Crystal structure of SMYD3 with diperodon R enantiomer bound to allosteric site==
<StructureSection load='6yuh' size='340' side='right'caption='[[6yuh]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6yuh]] 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=6YUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YUH 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]] 1.93&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=POW:Diperodon'>POW</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6yuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yuh OCA], [https://pdbe.org/6yuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yuh RCSB], [https://www.ebi.ac.uk/pdbsum/6yuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yuh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SMYD3_HUMAN SMYD3_HUMAN] Histone methyltransferase. Specifically methylates 'Lys-4' and 'Lys-5' of histone H3, inducing di- and tri-methylation, but not monomethylation. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.<ref>PMID:15235609</ref> <ref>PMID:22419068</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SMYD3 is a multifunctional epigenetic enzyme with lysine methyl transferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened using a biosensor-based competition assay. Diperodon was identified as an allosteric ligand. The ( R )-and ( S )-enantiomers of the racemic drug were isolated and their affinities determined ( K D &gt; = 42 and 84 muM). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although HSP90-SMYD3 binding was confirmed ( K D = 13 muM). The allosteric site appears to be druggable and suitable for exploration of non-catalytic SMYD3 functions and therapeutics with new mechanisms of action.

Discovery of an allosteric ligand binding site in SMYD3 lysine methyltransferase.,Talibov VO, Fabini E, FitzGerald E, Tedesco D, Eriksson D, Talu MJ, Rachman MM, Mihalic F, Manoni E, Naldi M, Sanese P, Forte G, Signorile ML, Barril X, Simone C, Bartolini M, Dobritzsch D, Del Rio A, Danielson UH Chembiochem. 2021 Jan 5. doi: 10.1002/cbic.202000736. PMID:33400854<ref>PMID:33400854</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yuh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cederfelt D]]
[[Category: Danielson UH]]
[[Category: Dobritzsch D]]
[[Category: Talibov VO]]