Structure of the histone deacetylase SIRT2.
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 A 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.
Finnin
M S
MS
Cellular Biochemistry and Biophysics Program, and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Donigian
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JR
Pavletich
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NP
D000595:Amino Acid Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; D009243:NAD; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D015032:Zinc