Crystal structure of a SIR2 homolog-NAD complex

Cell. 2001 Apr 20;105(2):269-79. doi: 10.1016/s0092-8674(01)00317-8.


The SIR2 protein family comprises a novel class of nicotinamide-adenine dinucleotide (NAD)-dependent protein deacetylases that function in transcriptional silencing, DNA repair, and life-span extension in Saccharomyces cerevisiae. Two crystal structures of a SIR2 homolog from Archaeoglobus fulgidus complexed with NAD have been determined at 2.1 A and 2.4 A resolutions. The structures reveal that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains. A distinct mode of NAD binding and an unusual configuration of the zinc ribbon motif are observed. The structures also provide important insights into the catalytic mechanism of NAD-dependent protein deacetylation by this family of enzymes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism
  • Archaeoglobus fulgidus / chemistry*
  • Archaeoglobus fulgidus / genetics
  • Binding Sites
  • Crystallography, X-Ray
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / chemistry*
  • NAD / metabolism
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae*
  • Sirtuin 2
  • Sirtuins
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Archaeal Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Trans-Activators
  • NAD
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases

Associated data

  • PDB/1ICI