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| | ==Crystal structure of cardiac specific histone methyltransferase SmyD1== | | ==Crystal structure of cardiac specific histone methyltransferase SmyD1== |
| - | <StructureSection load='3n71' size='340' side='right' caption='[[3n71]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3n71' size='340' side='right'caption='[[3n71]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n71]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N71 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N71 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n71]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N71 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SFG:SINEFUNGIN'>SFG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SFG:SINEFUNGIN'>SFG</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">mCG_127279, Smyd1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mCG_127279, Smyd1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3n71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n71 OCA], [http://pdbe.org/3n71 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n71 RCSB], [http://www.ebi.ac.uk/pdbsum/3n71 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n71 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=3n71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n71 OCA], [https://pdbe.org/3n71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n71 RCSB], [https://www.ebi.ac.uk/pdbsum/3n71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n71 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SMYD1_MOUSE SMYD1_MOUSE]] Methylates histone H3 at 'Lys-4' (H3K4me). Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis.<ref>PMID:11923873</ref> <ref>PMID:20943667</ref> | + | [[https://www.uniprot.org/uniprot/SMYD1_MOUSE SMYD1_MOUSE]] Methylates histone H3 at 'Lys-4' (H3K4me). Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis.<ref>PMID:11923873</ref> <ref>PMID:20943667</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Histone methyltransferase|Histone methyltransferase]] | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Sirinupong, N]] | | [[Category: Sirinupong, N]] |
| Structural highlights
Function
[SMYD1_MOUSE] Methylates histone H3 at 'Lys-4' (H3K4me). Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis.[1] [2]
Publication Abstract from PubMed
SmyD1 is a cardiac and muscle specific histone methyltransferase that methylates histone H3 at lysine 4 and regulates gene transcription in early heart development. The unique domain structure characterized by a 'spli' SET domain, a conserved MYND zinc finger, and a novel C-terminal domain (CTD) distinguishes SmyD1 from other SET domain containing methyltransferases. Here we report the crystal structure of full-length SmyD1 in complex with cofactor analog sinefungin at 2.3 A. The structure reveals that SmyD1 folds into a wrench-shaped structure with two thick 'grip' separated by a large, deep concave opening. Importantly, our structural and functional analysis suggests that SmyD1 appears to be regulated by an autoinhibition mechanism, and that unusually spacious target lysine-access channel and the presence of the CTD domain both negatively contribute to the regulation of this cardiovascularly relevant methyltransferase. Furthermore, our structure also provides structural basis for the interaction between SmyD1 and cardiac transcription factor skNAC, and suggests that the MYND domain may primarily serve as a protein interaction module and cooperate SmyD1 with skNAC to regulate cardiomyocyte growth and maturation. Overall, our data provide novel insights into the mechanism of SmyD1 regulation, which would be helpful in further understanding the role of this protein in heart development and cardiovascular diseases.
Crystal structure of cardiac specific histone methyltransferase SmyD1 reveals unusual active site architecture.,Sirinupong N, Brunzelle J, Ye J, Pirzada A, Nico L, Yang Z J Biol Chem. 2010 Oct 12. PMID:20943667[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gottlieb PD, Pierce SA, Sims RJ, Yamagishi H, Weihe EK, Harriss JV, Maika SD, Kuziel WA, King HL, Olson EN, Nakagawa O, Srivastava D. Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat Genet. 2002 May;31(1):25-32. Epub 2002 Apr 1. PMID:11923873 doi:http://dx.doi.org/10.1038/ng866
- ↑ Sirinupong N, Brunzelle J, Ye J, Pirzada A, Nico L, Yang Z. Crystal structure of cardiac specific histone methyltransferase SmyD1 reveals unusual active site architecture. J Biol Chem. 2010 Oct 12. PMID:20943667 doi:10.1074/jbc.M110.168187
- ↑ Sirinupong N, Brunzelle J, Ye J, Pirzada A, Nico L, Yang Z. Crystal structure of cardiac specific histone methyltransferase SmyD1 reveals unusual active site architecture. J Biol Chem. 2010 Oct 12. PMID:20943667 doi:10.1074/jbc.M110.168187
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