TY - JOUR
T1 - Structure of a Sir2 enzyme bound to an acetylated p53 peptide
AU - Avalos, Jose L.
AU - Celic, Ivana
AU - Muhammad, Shabazz
AU - Cosgrove, Michael S.
AU - Boeke, Jef D.
AU - Wolberger, Cynthia
PY - 2002/9/1
Y1 - 2002/9/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1097-2765(02)00628-7
DO - 10.1016/S1097-2765(02)00628-7
M3 - Article
C2 - 12408821
AN - SCOPUS:0036753953
VL - 10
SP - 523
EP - 535
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 3
ER -