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Crystal Structure of Histone Methyltransferase SUV39H2

Crystal Structure of Histone Methyltransferase SUV39H2. Hyun-Soo Cho Dept. of Biology Yonsei University. Histone Structure. Histone Modifications. - Different combinations of histone modifications, especially located near or within a gene’s promoter, may be VERY SPECIFIC to the

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Crystal Structure of Histone Methyltransferase SUV39H2

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  1. Crystal Structure of Histone Methyltransferase SUV39H2 Hyun-Soo Cho Dept. of Biology Yonsei University

  2. Histone Structure

  3. Histone Modifications - Different combinations of histone modifications, especially located near or within a gene’s promoter, may be VERY SPECIFIC to the transcriptional state of the gene

  4. Catalytic Mechanism of HMTase HMT Schematic diagram of the reaction. (ex. SET7/9 HMTase)

  5. Lysine Methyltransferases -use SAM (S-adenosylmethionine) -may give mono, di, tri-methyllysine -use direct displacement mechanisms

  6. DNA methyltransferase inhibitor 혈액암 환자 (임상 II상)유방암, 대장암세포 (FDA의 승인)

  7. Structure of MTase Inhibitors • Inhibitory activities of chaetocin against various HMT • Chaetocin is a competitive inhibitor for SU(VAR)3-9 and it is known to bind to Ado-Met binding site (Nat Chem Biol. 2005, 3, 143-145.).

  8. Human SET Domain Proteins DIM-5 of N. crassa Clr4 of S.pombe Kouzaride, T., (2002) Curr. Opin. Genet. Dev., 12, p198

  9. SUV39H2Suppressor of variegation 3-9 homolog 2 Cytoband: 10p13 Protein: 350 a.a. Cellular localization: nucleus Domain: CHROMO, Pre-SET,SET,Post-SET domain Function : Histone H3 lysine9 methyltransferase (Mol.cell.biol 2000) Expression in Cancer Semi-quantitative RT-PCR Esophageal cancer Normal esophagus Cell line Clinical sample B8814 ACTB Lung cancer Cell line Clinical sample SCC ADC SCC ADC Normal lung B8814 ACTB

  10. NusA fused SUV39H2 expression in insect cell system 1 2 3 4 5 6 7 8 9 Activity (fold) Enz conc (nM) Chromodomain Post-SET motif Activity (fold) Pre-SET motif SET domain 98 410 The Structured Construct Insect NusA-SUV39H2 E.Coli expressed SUV39H2

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