Cytidine deaminase (CDA), is one of the enzymes involved in the pyrimidine salvage pathways, which catalyzes
the formation of uridine and deoxyuridine by the hydrolytic deamination of cytidine and deoxycytidine, respectively.
Human CDA is a tetrameric enzyme of identical 15 kDa subunits, each containing an essential zinc atom in the active
site. The substrate binds to each active site independently and the cooperativity between subunits has not been reported.
CDA is able to recognize as substrates some antitumor and antiviral cytidine analogs rendering them pharmacologically
inactive. In light of the role played by this enzyme, a deep knowledge of CDA active site and mechanism of catalysis
is required. Site-directed mutagenesis, associated with molecular modeling studies, may be an important tool to
discover the active site structure of an enzyme and consequently its mechanism of action. In this review are summarized
the site-directed mutagenesis experiments performed on human CDA: through these studies it was possible to understand
the role exerted by specific amino acid residues in CDA active site and in the contacts between subunits. The obtained results
may open a way for designing new cytidine based drugs or more potent CDA inhibitors.