3n71 | pdb_00003n71

Crystal structure of cardiac specific histone methyltransferase SmyD1

spinqualitylabelsall models 3n71, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n71 is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MES, SFG, ZN Gene: mCG_127279, Smyd1 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SMYD1_MOUSE] Methylates histone H3 at 'Lys-4' (H3K4me). Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone methyltransferase 3D structures

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