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Literature summary for 2.3.1.B43 extracted from

  • Chang, J.H.; Kim, H.C.; Hwang, K.Y.; Lee, J.W.; Jackson, S.P.; Bell, S.D.; Cho, Y.
    Structural basis for the NAD-dependent deacetylase mechanism of Sir2 (2002), J. Biol. Chem., 277, 34489-34498.
    View publication on PubMed
Search for more literature for 2.3.1.B43

Crystallization (Commentary)

Crystallization (Comment) Organism
hanging drop vapor diffusion method at 4°C, crystal structure of wild-type enzyme, mutant enzyme S24A, mutant enzyme H80N, mutant enzyme F159A, and triple Sir2 mutant (D102G/F159A/R170A) Archaeoglobus fulgidus

Protein Variants

Protein Variants Comment Organism
D101N the decreased NAD-dependent deacetylase activity for the mutant proteins is at least partly due to reduced binding affinities for NAD+ Archaeoglobus fulgidus
F159A the Km value of the mutant enzyme is twice that of wild type enzyme, whereas the kcat is 5fold less. In the F159A mutant, two water molecules occupy the position of the Phe159 ring Archaeoglobus fulgidus
H80N mutant retains about 60% of the NAD binding ability of wild type Sir2 Archaeoglobus fulgidus
S24A the decreased NAD-dependent deacetylase activity for the mutant proteins is at least partly due to reduced binding affinities for NAD+ Archaeoglobus fulgidus

Organism

Organism UniProt Comment Textmining
Archaeoglobus fulgidus O28597
-
-

Purification (Commentary)

Purification (Comment) Organism
-
 Archaeoglobus fulgidus

Reaction

Reaction Comment Organism Reaction ID
NAD+ + [protein]-N6-acetyl-L-lysine = nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose crystallographic evidence is provided that 2'-O-acetyl ADP-ribose is a final product in the Sir2 reaction. A revised mechanism for catalysis based on the structural and functional characterization of Sir2 mutants is proposed. In this mechanism, the activation of the 2'-OH of nicotinamide ribose by His-116 is essential for the hydrolysis of the acetyl groups from N-acetyl lysine. The conserved Ser-24 and Asp-101 participate in the stabilization of local structure for NAD binding rather than direct involvement in catalysis Archaeoglobus fulgidus
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
NAD+ + [bovine serum albumin]-N6-acetyl-L-lysine crystallographic evidence is provided that 2'-O-acetyl ADP-ribose is a final product in the Sir2 reaction. A revised mechanism for catalysis based on the structural and functional characterization of Sir2 mutants is proposed. In this mechanism, the activation of the 2'-OH of nicotinamide ribose by His-116 is essential for the hydrolysis of the acetyl groups from N-acetyl lysine. The conserved Ser-24 and Asp-101 participate in the stabilization of local structure for NAD binding rather than direct involvement in catalysis Archaeoglobus fulgidus nicotinamide + [bovine serum albumin]-L-lysine + 2'-O-acetyl-ADP-ribose
-
 ?

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
50
-
 assay at Archaeoglobus fulgidus