Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294

Nature Structural and Molecular Biology

Volumn 16, Issue 3, 2009, Pages 312-317

  Chang, Yanqi ^a   Zhang, Xing ^a   Horton, John R ^a   Upadhyay, Anup K ^a   Spannhoff, Astrid ^b   Liu, Jin ^c   Snyder, James P ^c   Bedford, Mark T ^b   Cheng, Xiaodong ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS   (United States)

^c EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSYLHOMOCYSTEINASE; ARGININE; BIX 01294; G9A LIKE PROTEIN; HISTONE H3; HISTONE LYSINE METHYLTRANSFERASE; LYSINE; QUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CATALYSIS; COMPLEX FORMATION; CRYSTAL STRUCTURE; ENZYME SUBSTRATE; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING;

AZEPINES; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; HISTONE-LYSINE N-METHYLTRANSFERASE; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; QUINAZOLINES; S-ADENOSYLHOMOCYSTEINE;

EID: 62049083789     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.1560     Document Type: Article

References (37)

1. Jenuwein, T. The epigenetic magic of histone lysine methylation. FEBS J. 273, 3121-3135 (2006).
2. Grewal, S.I. & Jia, S. Heterochromatin revisited. Nat. Rev. Genet. 8, 35-46 (2007).
3. Tachibana, M. et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16, 1779-1791 (2002).
4. Tachibana, M. et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev. 19, 815-826 (2005).
5. McGarvey, K.M. et al. Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. Cancer Res. 66, 3541-3549 (2006).
6. Wozniak, R.J., Klimecki, W.T., Lau, S.S., Feinstein, Y. & Futscher, B.W. 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene 26, 77-90 (2007).
7. Yoo, C.B. et al. Delivery of 5-aza-2′-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res. 67, 6400-6408 (2007).
8. Kubicek, S. et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol. Cell 25, 473-481 (2007).
9. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676 (2006).
10. Shi, Y. et al. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525-528 (2008).
11. Feldman, N. et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat. Cell Biol. 8, 188-194 (2006).
12. Wu, H. et al. Crystal structure of catalytic domain of human euchromatic histone methyltransferase 1 in complex with SAH and dimethylated H3K9 peptide (PDB accession number 2RFI; doi:10.2210/pdb2rfi/pdb). (2007).
13. Peli, J. et al. Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the expression of Fas. EMBO J. 18, 1824-1831 (1999).
14. Gazin, C., Wajapeyee, N., Gobeil, S., Virbasius, C.M. & Green, M.R. An elaborate pathway required for Ras-mediated epigenetic silencing. Nature 449, 1073-1077 (2007).
15. Zhang, X. et al. Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase. Cell 111, 117-127 (2002).
16. Zhang, X. et al. Structural basis for the product specificity of histone lysine methyltransferases. Mol. Cell 12, 177-185 (2003).
17. Cheng, X., Collins, R.E. & Zhang, X. Structural and sequencemotifs of protein (histone) methylation enzymes. Annu. Rev. Biophys. Biomol. Struct. 34, 267-294 (2005).
18. Couture, J.F., Hauk, G., Thompson, M.J., Blackburn, G.M. & Trievel, R.C. Catalytic roles for carbon-oxygen hydrogen bonding in SET domain lysine methyltransferases. J. Biol. Chem. 281, 19280-19287 (2006).
19. Rathert, P. et al. Protein lysine methyltransferase G9a acts on non-histone targets. Nat. Chem. Biol. 4, 344-346 (2008).
20. Sampath, S.C. et al. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol. Cell 27, 596-608 (2007).
21. Pless, O. et al. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-β. J. Biol. Chem. 283, 26357-26363 (2008).
22. Chuikov, S. et al. Regulation of p53 activity through lysine methylation. Nature 432, 353-360 (2004).
23. Subramanian, K. et al. Regulation of estrogen receptor a by the SET7 lysine methyltransferase. Mol. Cell 30, 336-347 (2008).
24. Dong, K.B. et al. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity. EMBO J. 27, 2691-2701 (2008).
25. Epsztejn-Litman, S. et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat. Struct. Mol. Biol. 15, 1176-1183 (2008).
26. Tachibana, M., Matsumura, Y., Fukuda, M., Kimura, H. & Shinkai, Y. G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription. EMBO J. 27, 2681-2690 (2008).
27. Otwinowski, Z., Borek, D., Majewski, W. & Minor, W. Multiparametric scaling of diffraction intensities. Acta Crystallogr. A 59, 228-234 (2003).
28. Storoni, L.C., McCoy, A.J. & Read, R.J. Likelihood-enhanced fast rotation functions. Acta Crystallogr. D Biol. Crystallogr. 60, 432-438 (2004).
29. Jones, T.A., Zou, J.Y., Cowan, S.W. & Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110-119 (1991).
30. Brunger, A.T. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54, 905-921 (1998).
31. Schuttelkopf, A.W. & van Aalten, D.M. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 60, 1355-1363 (2004).
32. Collins, R.E. et al. In vitro and in vivo analyses of a Phe/Tyr switch controlling product specificity of histone lysine methyltransferases. J. Biol. Chem. 280, 5563-5570 (2005).
33. Meloun, M., Syrovy, T., Bordovska, S. & Vrana, A. Reliability and uncertainty in the estimation of pKa by least squares nonlinear regression analysis of multiwavelength spectrophotometric pH titration data. Anal. Bioanal. Chem. 387, 941-955 (2007).
34. Halgren, T.A. MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J. Comput. Chem. 20, 730-748 (1999).
35. Seetharaman, J. & Rajan, S.S. Crystal and molecular structure of noscapin. Zeitschrift fuer krystallographie 210, 111-113 (1995).
36. Friesner, R.A. et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47, 1739-1749 (2004).
37. Halgren, T.A. et al. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47, 1750-1759 (2004).