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 journalArticlepeer-review

    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

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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