Structure of a Sir2 Enzyme Bound to an Acetylated p53 Peptide

• Autores: Jose L. Avalos, Ivana Celic, Shabazz Muhammad, Michael S. Cosgrove, Jef D. Boeke, Cynthia Wolberger
• Localización: Molecular cell, ISSN 1097-2765, Vol. 9, Nº 3, 2002, págs. 523-535
• Idioma: inglés
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• Resumen

  • 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.