Crystal structure and functional analysis of the histone methyltransferase SET7/9 - PubMed (original) (raw)
Crystal structure and functional analysis of the histone methyltransferase SET7/9
Jonathan R Wilson et al. Cell. 2002.
Free article
Abstract
Methylation of lysine residues in the N-terminal tails of histones is thought to represent an important component of the mechanism that regulates chromatin structure. The evolutionarily conserved SET domain occurs in most proteins known to possess histone lysine methyltransferase activity. We present here the crystal structure of a large fragment of human SET7/9 that contains a N-terminal beta-sheet domain as well as the conserved SET domain. Mutagenesis identifies two residues in the C terminus of the protein that appear essential for catalytic activity toward lysine-4 of histone H3. Furthermore, we show how the cofactor AdoMet binds to this domain and present biochemical data supporting the role of invariant residues in catalysis, binding of AdoMet, and interactions with the peptide substrate.
Similar articles
- Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase.
Zhang X, Tamaru H, Khan SI, Horton JR, Keefe LJ, Selker EU, Cheng X. Zhang X, et al. Cell. 2002 Oct 4;111(1):117-27. doi: 10.1016/s0092-8674(02)00999-6. Cell. 2002. PMID: 12372305 Free PMC article. - Structures of SET domain proteins: protein lysine methyltransferases make their mark.
Yeates TO. Yeates TO. Cell. 2002 Oct 4;111(1):5-7. doi: 10.1016/s0092-8674(02)01010-3. Cell. 2002. PMID: 12372294 Review. - Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet.
Kwon T, Chang JH, Kwak E, Lee CW, Joachimiak A, Kim YC, Lee J, Cho Y. Kwon T, et al. EMBO J. 2003 Jan 15;22(2):292-303. doi: 10.1093/emboj/cdg025. EMBO J. 2003. PMID: 12514135 Free PMC article. - Structure and catalytic mechanism of the human histone methyltransferase SET7/9.
Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ. Xiao B, et al. Nature. 2003 Feb 6;421(6923):652-6. doi: 10.1038/nature01378. Epub 2003 Jan 22. Nature. 2003. PMID: 12540855 - SET domain protein lysine methyltransferases: Structure, specificity and catalysis.
Qian C, Zhou MM. Qian C, et al. Cell Mol Life Sci. 2006 Dec;63(23):2755-63. doi: 10.1007/s00018-006-6274-5. Cell Mol Life Sci. 2006. PMID: 17013555 Free PMC article. Review.
Cited by
- 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. Sirinupong N, et al. J Biol Chem. 2010 Dec 24;285(52):40635-44. doi: 10.1074/jbc.M110.168187. Epub 2010 Oct 12. J Biol Chem. 2010. PMID: 20943667 Free PMC article. - Metabolic defects provide a spark for the epigenetic switch in cancer.
Hitchler MJ, Domann FE. Hitchler MJ, et al. Free Radic Biol Med. 2009 Jul 15;47(2):115-27. doi: 10.1016/j.freeradbiomed.2009.04.010. Epub 2009 Apr 10. Free Radic Biol Med. 2009. PMID: 19362589 Free PMC article. Review. - Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein.
Carr SM, Munro S, Kessler B, Oppermann U, La Thangue NB. Carr SM, et al. EMBO J. 2011 Jan 19;30(2):317-27. doi: 10.1038/emboj.2010.311. Epub 2010 Nov 30. EMBO J. 2011. PMID: 21119616 Free PMC article. - SET/MYND Lysine Methyltransferases Regulate Gene Transcription and Protein Activity.
Leinhart K, Brown M. Leinhart K, et al. Genes (Basel). 2011 Feb 21;2(1):210-8. doi: 10.3390/genes2010210. Genes (Basel). 2011. PMID: 24710145 Free PMC article. - A continuous kinetic assay for protein and DNA methyltransferase enzymatic activities.
Duchin S, Vershinin Z, Levy D, Aharoni A. Duchin S, et al. Epigenetics Chromatin. 2015 Dec 15;8:56. doi: 10.1186/s13072-015-0048-y. eCollection 2015. Epigenetics Chromatin. 2015. PMID: 26675044 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases