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The active site of the SET domain is constructed on a knot

An Addendum to this article was published on 01 July 2003


The SET domain contains the catalytic center of lysine methyltransferases that target the N-terminal tails of histones and regulate chromatin function. Here we report the structure of the SET7/9 protein in the absence and presence of its cofactor product, S-adenosyl-L-homocysteine (AdoHcy). A knot within the SET domain helps form the methyltransferase active site, where AdoHcy binds and lysine methylation is likely to occur. A structure-guided comparison of sequences within the SET protein family suggests that the knot substructure and active site environment are conserved features of the SET domain.

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Figure 1: [1H-15N]-HSQC NMR spectra demonstrating the specific interactions of SET7/9 (residues 80–351) with AdoHcy and histone H3.
Figure 2: Three-dimensional structure of SET7/9.
Figure 3: SET7/9 binding to AdoHcy.
Figure 4: Structure-based sequence alignment of lysine HMT SET regions.

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We thank Y. Zhang for the clone of SET7 and C.D. Allis for encouragement and support. J.M.H. is a fellow of Rett Syndrome Research Foundation. This work was supported by an NIH grant to S.K.

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Correspondence to Sepideh Khorasanizadeh.

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Jacobs, S., Harp, J., Devarakonda, S. et al. The active site of the SET domain is constructed on a knot. Nat Struct Mol Biol 9, 833–838 (2002).

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