Old enzymes, new tricks: sirtuins are NAD(+)-dependent de-acylases

Abstract

Seven mammalian sirtuins are nicotinamide adenine dinucleotide (NAD)(+)-dependent deacetylases and are important modulators of energy metabolism and stress resistance. Two new studies by Du et al. (2011) and Peng et al. (2011) identify a new enzymatic activity for SIRT5, expanding the cellular repertoire of posttranslational modifications targeted by the sirtuins.

Figure 1. Molecular Phylogeny of the Sirtuins

(A) An unrooted tree diagram of a phylogenetic analysis of the conserved sirtuin core deacylase domain sequences, divided into class I, II, III, IV, and U groups; classes I and IV are further divided into subclasses indicated by lowercase letters. Adapted from Frye (2000). (B) Schematic of the conserved sirtuin core deacylase domains in human SIRT1–7, color coded to match the phylogenetic class from (A): green, class I; blue, class II; red, class III; yellow, class IV. Italic print indicates conservation of tyrosine (Y102) and arginine (R105) residues (numbering based on hSIRT5) required for the demalonylase and desuccinylase activities of hSIRT5.