Histone methyltransferase

From Proteopedia

Current revision

spinqualitylabelsall models Human histone-lysine N-methyltrasferase (magenta) complex with methylated lysine histone H3 peptide (green) and S-adenosyl homocysteine (SAH) (PDB entry 1o9s) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Disease 4 Structural highlights 5 3D Structures of histone methyltransferase Function Histone methyltransferase (HMT) are histone-lysine N-methyltransferase (KHMT) and histone-arginine N-methyltransferase (RHMT) which catalyzes the transfer of methyl groups to lysine and arginine residues of histones[1]. HMT use S-adenosyl methionine (SAM) or S-adenosyl homocysteine (SAH) as the methyl donor. KHMT can be SET domain-containing or non-SET domain-containing. The SET domain contains the catalytic core of KHMT and targets the lysine tail region of KHMT. CxxC domain is a zinc finger domain. For SET7/9 see Histone Lysine Methyltransferase SET7/9. euchromatin histone methyltransferase dimethylates histone H3 at Lys 9 resulting in transcriptional repression[2]. DOT1L histone methyltransferase methylates histone H3 at Lys 79 resulting in transcriptional repression[3]. Relevance Inhibitors of the histone-lysine N-methyltransferase SMYD2 which represses the tumor-suppressing activities of p53 are studied as cancer therapy drugs[4]. Disease Aberrant HMT plays a role in cancer, intellectual disability syndromes and regulation of tissue aging[5]. Structural highlights Human inserted in a hydrophobic environment[6]. Water molecules shown as red spheres 3D Structures of histone methyltransferase Histone methyltransferase 3D structures

References

1. ↑ Trievel RC. Structure and function of histone methyltransferases. Crit Rev Eukaryot Gene Expr. 2004;14(3):147-69. PMID:15248813
2. ↑ Hwang S, Kim S, Kim K, Yeom J, Park S, Kim I. Euchromatin histone methyltransferase II (EHMT2) regulates the expression of ras-related GTP binding C (RRAGC) protein. BMB Rep. 2020 Nov;53(11):576-581. PMID:32684241 doi:10.5483/BMBRep.2020.53.11.055
3. ↑ Alexandrova E, Salvati A, Pecoraro G, Lamberti J, Melone V, Sellitto A, Rizzo F, Giurato G, Tarallo R, Nassa G, Weisz A. Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors. Front Genet. 2022 Apr 13;13:864612. PMID:35495127 doi:10.3389/fgene.2022.864612
4. ↑ Ferguson AD, Larsen NA, Howard T, Pollard H, Green I, Grande C, Cheung T, Garcia-Arenas R, Cowen S, Wu J, Godin R, Chen H, Keen N. Structural Basis of Substrate Methylation and Inhibition of SMYD2. Structure. 2011 Jul 20. PMID:21782458 doi:10.1016/j.str.2011.06.011
5. ↑ Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012 Apr 3;13(5):343-57. doi: 10.1038/nrg3173. PMID:22473383 doi:http://dx.doi.org/10.1038/nrg3173
6. ↑ Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. Epub 2003 Jan 22. PMID:12540855 doi:10.1038/nature01378