Structure of the histone deacetylase SIRT2 Journal Article
| Authors: | Finnin, M. S.; Donigian, J. R.; Pavletich, N. P. |
| Article Title: | Structure of the histone deacetylase SIRT2 |
| 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. |
| Keywords: | unclassified drug; gene cluster; protein domain; telomere; cluster analysis; protein binding; gene locus; gene product; genetic transcription; cloning, molecular; gene mapping; transcription regulation; amino acid sequence; conserved sequence; molecular sequence data; sequence homology, amino acid; brain; sequence alignment; binding site; amino acid; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; trans-activators; caenorhabditis elegans; gene silencing; catalysis; protein folding; zinc; enzyme structure; histone deacetylases; protein structure, secondary; mutagenesis; nad; histone deacetylase; lifespan; nicotinamide adenine dinucleotide; ribosome; hydrophobicity; sirtuins; humans; priority journal; article; silent information regulator proteins, saccharomyces cerevisiae; protein silent information regulator 2 |
| Journal Title: | Nature Structural Biology |
| Volume: | 8 |
| Issue: | 7 |
| ISSN: | 1072-8368 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-07-01 |
| Start Page: | 621 |
| End Page: | 625 |
| Language: | English |
| DOI: | 10.1038/89668 |
| PUBMED: | 11427894 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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