Structure and autoregulation of the yeast Hst2 homolog of Sir2.
Yeast Hst2 (yHst2) is a member of the silencing information regulator 2 (Sir2) family of NAD(+)-dependent protein deacetylases that are implicated in transcriptional silencing, DNA repair, genome stability and longevity. The X-ray crystal structure of the full-length yHst2 protein reveals a central catalytic core domain fold that is characteristic of the other Sir2 homologs, and C- and N-terminal extensions that interact with the NAD(+) and acetyl-lysine substrate-binding sites, respectively, suggesting an autoregulatory function for these domains. Moreover, the N-terminal extension mediates formation of a homotrimer within the crystal lattice. Enzymatic and sedimentation equilibrium studies using deletion constructs of yHst2 support the involvement of the N- and C-terminal yHst2 regions and trimer formation in catalysis by yHst2. Together, these studies indicate that the sequence-divergent N- and C-terminal regions of the eukaryotic Sir2 proteins may have a particularly important role in their distinct substrate-binding properties, biological activities or both.
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D007700:Kinetics; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000737:chemistry* / Q000378:metabolism
D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; C423033:HST2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins