6p7z: Difference between revisions

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<StructureSection load='6p7z' size='340' side='right'caption='[[6p7z]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
<StructureSection load='6p7z' size='340' side='right'caption='[[6p7z]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6p7z]] 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=6P7Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P7Z FirstGlance]. <br>
<table><tr><td colspan='2'>[[6p7z]] 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=6P7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P7Z FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=O41:5-cyclopropyl-N-[1-(methylsulfonyl)piperidin-4-yl]-1,2-oxazole-3-carboxamide'>O41</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]] 1.19&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6p6g|6p6g]], [[6p6k|6p6k]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=O41:5-cyclopropyl-N-[1-(methylsulfonyl)piperidin-4-yl]-1,2-oxazole-3-carboxamide'>O41</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6p7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p7z OCA], [https://pdbe.org/6p7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p7z RCSB], [https://www.ebi.ac.uk/pdbsum/6p7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p7z ProSAT]</span></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=6p7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p7z OCA], [http://pdbe.org/6p7z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p7z RCSB], [http://www.ebi.ac.uk/pdbsum/6p7z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p7z ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>
[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 ==
We report herein the discovery of isoxazole amides as potent and selective SET and MYND Domain-Containing Protein 3 (SMYD3) inhibitors. Elucidation of the structure-activity relationship of the high-throughput screening (HTS) lead compound 1 provided potent and selective SMYD3 inhibitors. The SAR optimization, cocrystal structures of small molecules with SMYD3, and mode of inhibition (MOI) characterization of compounds are described. The synthesis and biological and pharmacokinetic profiles of compounds are also presented.


Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors.,Su DS, Qu J, Schulz M, Blackledge CW, Yu H, Zeng J, Burgess J, Reif A, Stern M, Nagarajan R, Pappalardi MB, Wong K, Graves AP, Bonnette W, Wang L, Elkins P, Knapp-Reed B, Carson JD, McHugh C, Mohammad H, Kruger R, Luengo J, Heerding DA, Creasy CL ACS Med Chem Lett. 2019 Dec 27;11(2):133-140. doi:, 10.1021/acsmedchemlett.9b00493. eCollection 2020 Feb 13. PMID:32071679<ref>PMID:32071679</ref>
==See Also==
 
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6p7z" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Histone-lysine N-methyltransferase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bonnette, W G]]
[[Category: Bonnette WG]]
[[Category: Elkins, P A]]
[[Category: Elkins PA]]
[[Category: Inhibitor]]
[[Category: Methyltransferase]]
[[Category: Oncology]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 17:54, 13 March 2024

Co-crystal Structure of human SMYD3 with Isoxazole Amides InhibitorsCo-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors

Structural highlights

6p7z 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 1.19Å
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

6p7z, resolution 1.19Å

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