View source for 5ccm


==Crystal structure of SMYD3 with SAM and EPZ030456==
<StructureSection load='5ccm' size='340' side='right'caption='[[5ccm]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ccm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CCM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4ZX:6-CHLORANYL-2-OXIDANYLIDENE-N-[(1S,5R)-8-[4-[(PHENYLMETHYL)AMINO]PIPERIDIN-1-YL]SULFONYL-8-AZABICYCLO[3.2.1]OCTAN-3-YL]-1,3-DIHYDROINDOLE-5-CARBOXAMIDE'>4ZX</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ccl|5ccl]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMYD3, ZMYND1, ZNFN3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ccm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ccm OCA], [http://pdbe.org/5ccm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ccm RCSB], [http://www.ebi.ac.uk/pdbsum/5ccm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ccm ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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 has been implicated in a range of cancers; however, until now no potent selective small molecule inhibitors have been available for target validation studies. A novel oxindole series of SMYD3 inhibitors was identified through screening of the Epizyme proprietary histone methyltransferase-biased library. Potency optimization afforded two tool compounds, sulfonamide EPZ031686 and sulfamide EPZ030456, with cellular potency at a level sufficient to probe the in vitro biology of SMYD3 inhibition. EPZ031686 shows good bioavailability following oral dosing in mice making it a suitable tool for potential in vivo target validation studies.

Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor.,Mitchell LH, Boriack-Sjodin PA, Smith S, Thomenius M, Rioux N, Munchhof M, Mills JE, Klaus C, Totman J, Riera TV, Raimondi A, Jacques SL, West K, Foley M, Waters NJ, Kuntz KW, Wigle TJ, Scott MP, Copeland RA, Smith JJ, Chesworth R ACS Med Chem Lett. 2015 Aug 27;7(2):134-8. doi: 10.1021/acsmedchemlett.5b00272., eCollection 2016 Feb 11. PMID:26985287<ref>PMID:26985287</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ccm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone-lysine N-methyltransferase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Boriack-Sjodin, P A]]
[[Category: Drug discovery]]
[[Category: Epigenetic]]
[[Category: Methyltransferase]]
[[Category: Protein-inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]