Abstract.
Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins that contain the evolutionarily conserved SET domain and plays a fundamental role in epigenetic regulation of gene activation and silencing in all eukaryotes. The recently determined three-dimensional structures of the SET domains from chromosomal proteins reveal that the core SET domain structure contains a two-domain architecture, consisting of a conserved anti-parallel β-barrel and a structurally variable insert that surround a unusual knot-like structure that comprises the enzyme active site. These structures of the SET domains, either in the free state or when bound to cofactor S-adenosyl-L-homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate complex, further yield the structural insights into the molecular basis of the substrate specificity, methylation multiplicity and the catalytic mechanism of histone lysine methylation.
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Received 10 June 2006; accepted 22 August 2006
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Qian, C., Zhou, M.M. SET domain protein lysine methyltransferases: Structure, specificity and catalysis. Cell. Mol. Life Sci. 63, 2755–2763 (2006). https://doi.org/10.1007/s00018-006-6274-5
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DOI: https://doi.org/10.1007/s00018-006-6274-5