Accepted name: protein acetyllysine N-acetyltransferase
Reaction: [protein]-N6-acetyl-L-lysine + NAD+ + H2O = [protein]-L-lysine + 2′′-O-acetyl-ADP-D-ribose + nicotinamide (overall reaction)
(1a) [protein]-N6-acetyl-L-lysine + NAD+ = [protein]-N6-[1,1-(5-adenosylyl-α-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + nicotinamide
(1b) [protein]-N6-[1,1-(5-adenosylyl-α-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + H2O = [protein]-L-lysine + 2′′-O-acetyl-ADP-D-ribose
Other name(s): Sir2; protein lysine deacetylase; NAD+-dependent protein deacetylase
Systematic name: [protein]-N6-acetyl-L-lysine:NAD+ N-acetyltransferase (NAD+-hydrolysing; 2′′-O-acetyl-ADP-D-ribose-forming)
Comments: The enzyme, found in all domains of life, is involved in gene regulation by deacetylating proteins. Some of the 2′′-O-acetyl-ADP-D-ribose converts non-enzymically to 3′′-O-acetyl-ADP-D-ribose.
1.  Landry, J., Slama, J.T. and Sternglanz, R. Role of NAD+ in the deacetylase activity of the SIR2-like proteins. Biochem. Biophys. Res. Commun. 278 (2000) 685–690. [PMID: 11095969]
2.  Sauve, A.A., Celic, I., Avalos, J., Deng, H., Boeke, J.D. and Schramm, V.L. Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions. Biochemistry 40 (2001) 15456–15463. [PMID: 11747420]
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[EC created 2019]