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Substrate recognition in lysine deacetylases (769.7)
Author(s) -
Toro Tasha,
Painter Richard,
Garrett Destane,
Watt Terry
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.769.7
Subject(s) - lysine , acetylation , context (archaeology) , biochemistry , substrate (aquarium) , chemistry , computational biology , amino acid , biology , gene , paleontology , ecology
Protein acetylation is a widely used cell signaling mechanism which reversibly regulates many cellular processes. Lysine deacetylases (KDACs) catalyze the hydrolysis of ε‐N‐acetyl lysine residues to generate an unmodified lysine and acetate. Perturbations in this process have been linked to diseases, including cancer and inflammation. Thousands of acetylated proteins have been identified, but little is known about how proteins are deacetylated. We aim to understand how individual KDACs recognize their preferred substrates. Assays performed using standard commercial reagents and acetylated peptides as substrates suggest that KDACs and their variants have unique specificity profiles. To better understand this in a biologically relevant context, we have engineered model proteins which more closely resemble natural KDAC substrates. Each is a fixed scaffold that contains a single acetylated lysine in a defined variable sequence and secondary structure. Binding and activity for KDAC‐substrate pairs are used to determine KDAC substrate preference and specificity. By combining these results with structural data and molecular modeling, we will gain insights into the mechanism of KDAC substrate recognition. Grant Funding Source : Supported by Louisiana Cancer Research Consortium, NIH #8G12MD007595‐05, DoD W911NF‐13‐1‐0129