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Structural, Mutational, And Kinetic Characterization Of Ura4, An Isocytosine Deaminase, Ashlee Hoffman Jan 2023

Structural, Mutational, And Kinetic Characterization Of Ura4, An Isocytosine Deaminase, Ashlee Hoffman

WWU Graduate School Collection

Cytosine Deaminases (CD) are a class of enzymes found in prokaryotes and fungi that have been studied in the past due to their ability to deaminate the prodrug 5-fluorocytosine (5-FC) producing 5-fluorouracil (5-FU). 5-FU is a common anti-cancer drug that can inhibit DNA synthesis leading to cancer cell death. 5-fluorocytosine can interact with digestive bacteria leading to unwanted side effects for cancer patients. Isocytosine Deaminases (ICD) are enzymes that are of interest in the treatment of cancers using Gene Directed Enzyme Prodrug Therapy (GDEPT). ICDs can deaminate the prodrug 5-fluoroisocytosine (5-FIC) also producing the drug 5-FU.  5-FIC will likely not …