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Structure of the histone deacetylase SIRT2

Nature Structural Biology volume 8, pages 621–625 (2001)Cite this article

Abstract

Sir2 is an NAD-dependent histone deacetylase that mediates transcriptional silencing at mating-type loci, telomeres and ribosomal gene clusters, and has a critical role in the determination of life span in yeast and Caenorhabditis elegans. The 1.7 Å crystal structure of the 323 amino acid catalytic core of human SIRT2, a homolog of yeast Sir2, reveals an NAD-binding domain, which is a variant of the Rossmann fold, and a smaller domain composed of a helical module and a zinc-binding module. A conserved large groove at the interface of the two domains is the likely site of catalysis based on mutagenesis. Intersecting this large groove, there is a pocket formed by the helical module. The pocket is lined with hydrophobic residues conserved within each of the five Sir2 classes, suggesting that it is a class-specific protein-binding site.

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Figure 1: The structure of SIRT2.
Figure 2: Sequence conservation among the Sir2 family of enzymes.
Figure 3: Conservation among Sir2-like enzymes.
Figure 4: Structural comparison between SIRT2 and Sir2-Af1.

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Acknowledgements

We thank V.M. Richon for the gift of the [3H]acetyl-labeled murine erythroleukemia cell-derived histone substrate; H. Erdument-Bromage of the Sloan-Kettering Microchemistry Facility for N-terminal sequence and mass spectroscopic analysis; C. Murray for administrative assistance; and the staff of the Cornell High Energy Synchotron Source MacChess for help with data collection. Supported by the NIH, the Howard Hughes Medical Institute, the Dewitt Wallace Foundation, the Samuel and May Rudin Foundation and the Rochelle Belfer Foundation.

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  1. Jill R. Donigian

    Present address: The Rockefeller University, New York, New York, 10021, USA

Authors and Affiliations

  1. Cellular Biochemistry and Biophysics Program, and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Michael S. Finnin, Jill R. Donigian & Nikola P. Pavletich

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  1. Michael S. Finnin
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Correspondence to Nikola P. Pavletich.

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Finnin, M., Donigian, J. & Pavletich, N. Structure of the histone deacetylase SIRT2. Nat Struct Mol Biol 8, 621–625 (2001). https://doi.org/10.1038/89668

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