5ccm: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5ccm]] 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=5CCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CCM FirstGlance]. <br>
<table><tr><td colspan='2'>[[5ccm]] 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=5CCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CCM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ccm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ccm OCA], [https://pdbe.org/5ccm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ccm RCSB], [https://www.ebi.ac.uk/pdbsum/5ccm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ccm ProSAT]</span></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=5ccm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ccm OCA], [https://pdbe.org/5ccm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ccm RCSB], [https://www.ebi.ac.uk/pdbsum/5ccm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ccm ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>  
[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 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==
==See Also==

Latest revision as of 15:20, 6 March 2024

Crystal structure of SMYD3 with SAM and EPZ030456Crystal structure of SMYD3 with SAM and EPZ030456

Structural highlights

5ccm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2]

See Also

References

  1. ↑ Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004 Aug;6(8):731-40. Epub 2004 Jul 4. PMID:15235609 doi:10.1038/ncb1151
  2. ↑ Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF, McDevitt P, Sinnamon R, Le B, Mas G, Annan R, Sage J, Garcia BA, Tummino PJ, Gozani O, Kruger RG. Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics. 2012 Apr;7(4):340-3. doi: 10.4161/epi.19506. Epub 2012 Apr 1. PMID:22419068 doi:10.4161/epi.19506

5ccm, resolution 2.30Å

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