Reference: Avalos JL, et al. (2002) Structure of a Sir2 enzyme bound to an acetylated p53 peptide. Mol Cell 10(3):523-35

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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 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.

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Journal Article | Research Support, U.S. Gov't, P.H.S.
Authors
Avalos JL, Celic I, Muhammad S, Cosgrove MS, Boeke JD, Wolberger C
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