Structure of a Sir2 enzyme bound to an acetylated p53 peptide

Mol Cell. 2002 Sep;10(3):523-35. doi: 10.1016/s1097-2765(02)00628-7.


Sir2 proteins are NAD(+)-dependent protein deacetylases that play key roles in transcriptional regulation, DNA repair, and life span regulation. The structure of an archaeal Sir2 enzyme, Sir2-Af2, bound to an acetylated p53 peptide reveals that the substrate binds in a cleft in the enzyme, forming an enzyme-substrate beta sheet with two flanking strands in Sir2-Af2. The acetyl-lysine inserts into a conserved hydrophobic tunnel that contains the active site histidine. Comparison with other structures of Sir2 enzymes suggests that the apoenzyme undergoes a conformational change upon substrate binding. Based on the Sir2-Af2 substrate complex structure, mutations were made in the other A. fulgidus sirtuin, Sir2-Af1, that increased its affinity for the p53 peptide.

Publication types

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

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Archaeoglobus fulgidus / enzymology
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Peptides / chemistry*
  • Peptides / metabolism
  • Protein Binding
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Sirtuins / chemistry*
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Archaeal Proteins
  • Peptides
  • Tumor Suppressor Protein p53
  • Sirtuins

Associated data

  • PDB/1MA3