Explore SIRT5 new enzymatic activity by protein structure analysis
BUCT Science Mansion 302
Abstract: Histones are acetylated and deacetylated on lysine residues in the N-terminal tail, and on the surface of the nucleosome core as part of gene regulation. Typically, these reactions are catalyzed by enzymes with HAT or HDAC activity. The NAD-dependent deacetylases, sirtuins, have been identified as important regulators of diverse biological processes, including life span, transcription, cell survival, and metabolism. Of the seven human sirtuins, only three of them, SIRT1, SIRT2 and SIRT3, have robust deacetylation activities in vitro and in vivo. The remaining sirtuins have either no detectable or very weak deacetylation activity in vitro. Our study showed that SIRT5 is an efficient desuccinylase and demalonylase in vitro, catalyzing the hydrolysis of succinyl lysine and malonyl lysine residues. The preference for succinyl and malonyl groups can be explained by the presence of an arginine (R105) and tyrosine (Y102) residue in the acyl pocket of SIRT5, which is typically occupied by hydrophobic residues in sirtuins with robust deacetylation activity.