Mechanism of Sirt1 NAD+-dependent Protein Deacetylase Inhibition by Cysteine S-Nitrosation.

ABSTRACT: The sirtuin family of proteins catalyze the NAD⁺-dependent deacylation of acyl-lysine residues. Humans encode seven sirtuins (Sirt1-7), and recent studies have suggested that post-translational modification of Sirt1 by cysteine S-nitrosation correlates with increased acetylation of Sirt1 deacetylase substrates. However, the mechanism of Sirt1 inhibition by S-nitrosation was unknown. Here, we show that Sirt1 is transnitrosated and inhibited by the physiologically relevant nitrosothiol S-nitrosoglutathione. Steady-state kinetic analyses and binding assays were consistent with Sirt1 S-nitrosation inhibiting binding of both the NAD⁺ and acetyl-lysine substrates. Sirt1 S-nitrosation correlated with Zn²⁺ release from the conserved sirtuin Zn²⁺-tetrathi

SUBMITTER: Kalous KS 

PROVIDER: S-EPMC5207242 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature