Kinetic and Structural Basis for Acyl-Group Selectivity and NAD(+) Dependence in Sirtuin-Catalyzed Deacylation.

ABSTRACT: Acylation of lysine is an important protein modification regulating diverse biological processes. It was recently demonstrated that members of the human Sirtuin family are capable of catalyzing long chain deacylation, in addition to the well-known NAD(+)-dependent deacetylation activity [Feldman, J. L., Baeza, J., and Denu, J. M. (2013) J. Biol. Chem. 288, 31350-31356]. Here we provide a detailed kinetic and structural analysis that describes the interdependence of NAD(+)-binding and acyl-group selectivity for a diverse series of human Sirtuins, SIRT1-SIRT3 and SIRT6. Steady-state and rapid-quench kinetic analyses indicated that differences in NAD(+) saturation and susceptibility to nicotinamide inhibition reflect unique kinetic behavior displayed by each Sirtuin and depend on acyl substra

SUBMITTER: Feldman JL 

PROVIDER: S-EPMC4470489 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature