<br/>Lysine deacetylases (KDACs) are enzymes that regulate the post translational modification of lysine by acetate. KDACs serve an important role in numerous biological processes as well as diseases such as asthma, diabetes, and certain cancers. Unlike most KDACs, KDAC6 contains two catalytic domains. We hypothesize that the catalytic domains of KDAC6 will catalyze the deacetylation reaction independently, with each domain having several distinct substrates. KDAC activity is detected by fluorescence based assays or mass spectrometry. We are studying the activity using in vitro assays and by mutating the KDAC6 gene in HEK293T cells to evaluate changes in acetylated proteins. These assays will allow us to understand the contributions of substrate features and each of the KDAC6 catalytic domains to substrate specificity. The first catalytic domain is inactive with some substrates of the full length protein, and therefore the catalytic domain 1 of KDAC6 alone cannot reproduce the activity of the full length protein. In combination with the cellular data, these data will result in the identification of more substrates for KDAC6 along with the effects of changes in activity of KDAC6 with proteins in living cells.

KDAC6: Catalytic domain substrate specificity

255th National Meeting (2018)

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