The Effect of Substrate Length on Lysine Deacetylase Activity

Lysine deacetylases (KDACs) are proteins involved in regulating post-translational modification of lysine residues in proteins. Anomalous acetylation of lysine has been linked to numerous diseases, and unusual activity of lysine deacetylases often appears to be a causative factor. Our goal is to understand the substrate specificity of metal-dependent KDACs. Here we are specifically interested in the correlation between KDAC activity with peptides derived from acetylated proteins and the activity of the same KDAC with the corresponding full-length substrate proteins. Activity with peptides is determined by both label-free fluorescence assays and mass spectrometry. Initial results with peptides, each derived from a single source protein but of varying length of sequence on either side of the acetylated lysine, did not reveal a correlation between peptide length and KDAC activity. The absence of such a correlation suggests important contributions from secondary structure of the substrate protein and/or contr...