Lysine Deacetylase Substrate Selectivity: A Dynamic Ionic Interaction Specific to KDAC8.

ABSTRACT: Lysine acetylation and deacetylation are critical for regulation of many cellular proteins. Despite the importance of this cycle, it is unclear how lysine deacetylase (KDAC) family members discriminate between acetylated proteins to react with a discrete set of substrates. Potential short-range interactions between KDAC8 and a known biologically relevant peptide substrate were identified using molecular dynamics (MD) simulations. Activity assays with a panel of peptides derived from this substrate supported a putative ionic interaction between arginine at the -1 substrate position and KDAC8 D101. Additional assays and MD simulations confirmed this novel interaction, which promotes deacetylation of substrates. Verification that a negatively charged residue at the 101 position is necessary f

SUBMITTER: Toro TB 

PROVIDER: S-EPMC8408915 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature