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

Nature Structural Biology volume 9, pages 833–838 (2002)Cite this article

An Addendum to this article was published on 01 July 2003

Abstract

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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GenBank/EMBL/DDBJ

Protein Data Bank

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Acknowledgements

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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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, 22908, Virginia, USA

    Steven A. Jacobs, Joel M. Harp, Fraydoon Rastinejad & Sepideh Khorasanizadeh

  2. Department of Pharmacology, University of Virginia Health System, Charlottesville, 22908, Virginia, USA

    Srikripa Devarakonda & Fraydoon Rastinejad

  3. Biosciences Division/Structural Biology Center, Argonne National Laboratory, Argonne, 60439, Illinois, USA

    Youngchang Kim

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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). https://doi.org/10.1038/nsb861

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