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 language | English (US) |
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Pages (from-to) | 523-535 |
Number of pages | 13 |
Journal | Molecular Cell |
Volume | 10 |
Issue number | 3 |
DOIs | |
State | Published - Sep 1 2002 |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology