Protein lysine desuccinylase and demalonylase activity of Sirt5.

© 2011 EPFL
© 2011 EPFL
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase. Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. The group of Johan Auwerx ( Laboratory of Integrative Systems Physiology LISP) together with several colleagues from Cornell and the University of Hong Kong found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg105) and tyrosine residue (Tyr102) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications.
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