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Description
Lysine deacetylases (KDACs) are enzymes that remove an acetyl group from a lysine, thereby regulating the post translational modification of lysine. KDACs are important in many different biological processes and are associated with various mechanisms of diseases in the human body. Peptides of putative substrate proteins were screened for activity with KDAC8 using a combination of fluorescence based and mass spectroscopic methods. The rate of reaction varies based on the amino acids adjacent to the acetylated lysine. Our results also suggest that KDAC8 has high enzymatic activity with multiply acetylated substrates. Correlation of activity data with molecular dynamics simulations suggests that a specific residue, Y100, is important in substrate determination. Our results support the possibility that some, but not all, of the putative substrate proteins are actual substrates of KDAC8. In addition to identifying peptides that react with certain KDACs, we have identified some of the interactions between the peptides and KDAC8 that contribute to substrate selectivity. Future plans include determining which acetyl group is removed first from multiply acetylated substrates and characterizing the interaction of Y100 with substrates using mutations that mimic the corresponding residue present in other KDACs.
Publication Date
2021
City
New Orleans
Keywords
KDAC8, Putative Substrates, Peptides
Disciplines
Biology | Cell and Developmental Biology | Laboratory and Basic Science Research | Life Sciences | Research Methods in Life Sciences
Recommended Citation
Bezue, Jada A.; Toro, Tasha B.; and Watt, Terry J., "Evaluating Specificity of KDAC8 with Putative Substrates" (2021). Festival of Scholars. 10.
https://digitalcommons.xula.edu/xula_fos/10
Included in
Biology Commons, Cell and Developmental Biology Commons, Laboratory and Basic Science Research Commons, Research Methods in Life Sciences Commons