Cytosine deaminase (CDA) (CDA)

Cytosine deaminase (CDA) is an enzyme that catalyzes the hydrolytic deamination of cytosine to uracil and ammonia. It is primarily found in bacteria and fungi and is notably absent in higher eukaryotes, including humans. This absence makes CDA a valuable tool in suicide gene therapy for cancer, where the enzyme is delivered to tumor cells to convert the non-toxic prodrug 5-fluorocytosine (5-FC) into the potent chemotherapeutic 5-fluorouracil (5-FU). Phosphonocytosine is a well-known transition state analog and potent inhibitor of this enzyme, used to study its catalytic mechanism and structural biology. By mimicking the tetrahedral intermediate of the reaction, phosphonocytosine provides insights into the active site architecture, facilitating the engineering of CDA variants with improved therapeutic properties.

Other names

Cytosine aminohydrolaseCodAbCDyCDCytosine deaminase (CDA)

Cytosine deaminase converts the prodrug 5-fluorocytosine into 5-fluorouracil, which is then converted to 5-FdUMP, a suicide inhibitor of thymidylate synthase, thereby inhibiting DNA synthesis and inducing apoptosis.