Structure of a Sir2 Enzyme Bound to an Acetylated p53 Peptide.
Avalos JL, Celic I, Muhammad S, Cosgrove MS, Boeke JD, Wolberger C
Molecular Cell (2002)
Category: chromatin structure ¤ Added: Sep 27, 2002 ¤ Rating: ◊◊
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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