Structure of a Sir2 enzyme bound to an acetylated p53 peptide

Jose L. Avalos, Ivana Celic, Shabazz Muhammad, Michael S. Cosgrove, Jef D. Boeke, Cynthia Wolberger

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

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 β 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.

Original languageEnglish (US)
Pages (from-to)523-535
Number of pages13
JournalMolecular Cell
Volume10
Issue number3
DOIs
StatePublished - Sep 1 2002

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Avalos, J. L., Celic, I., Muhammad, S., Cosgrove, M. S., Boeke, J. D., & Wolberger, C. (2002). Structure of a Sir2 enzyme bound to an acetylated p53 peptide. Molecular Cell, 10(3), 523-535. https://doi.org/10.1016/S1097-2765(02)00628-7