Enzyme - Cytidine deaminase

Alternative Name(s)
  • Cytosine nucleoside deaminase.
  • Cytidine aminohydrolase.
  • (Deoxy)cytidine deaminase.

Catalytic Activity

2'-deoxycytidine + H(+) + H2O = 2'-deoxyuridine + NH4(+)



Reaction Mechanism

    Cytosine deaminase (CD) catalyses the deamination of cytosine, producing uracil. This enzyme is present in prokaryotes and fungi (but not multicellular eukaryotes) and is an important member of the pyrimidine salvage pathway in those organisms. The enzyme is of widespread interest both for antimicrobial drug design and for gene therapy applications against tumours.

    The full catalytic cycle is composed of three major steps, including the substrate (cytosine) binding, the release of ammonia and the departure of the product (uracil) from the active site.

    The catalytic zinc ion is bound to His102, Cys129, Cys132, and a catalytic water. The positive charge of the metal ion polarises the O-H bond in water, increasing its acidity towards the close proximity Glu104. Thus, the first step involved the proton transfer from the zinc-bound water to Glu104, the rotation of the carboxyl group of Glu104 and the proton transfer from the protonated Glu104 to cytosine. The subsequent nucleophilic attack at the C2 of the substrate by the resulting hydroxide anion leads to a tetrahedral intermediate. The second step concerns the formation of both ammonia and uracil. Once again this steps involves the proton transfers from the zinc-bound hydroxide anion to Glu104 and from Glu104 to the amine group which are stepwise rather than synchronous as in the first step. This step forms ammonia and uracil. Uracil remains strongly bound to the zinc metal. The final step consists of several proton transfers shuttled by Glu104 and one nucleophilic attack. One water molecule, which replaces the ammonia from the second step, heterolytically splits with its proton going to Glu104 and the hydroxide anion synchronously attacking C2 of uracil.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Cys P0ABF6 132 1ctt 132
    His P0ABF6 102 1ctt 102
    Glu P0ABF6 104 1ctt 104
    Cys P0ABF6 129 1ctt 129
    Step Components

    proton transfer, unimolecular elimination by the conjugate base, bimolecular nucleophilic addition, native state of enzyme regenerated, deamination

    Step 1.

    Glu104 deprotonates water.

    Step 2.

    This step may well occur in a concerted manner with step 1. Glu104 rotates in the active site and donates its proton to the cytidine substrate.

    Step 3.

    Activated water initiates a nucleophilic attack on the substrate in an addition reaction.

    Step 4.

    Glu104 deprotonates the added hydroxyl group.

    Step 5.

    The oxyanion collapses, eliminating ammonia with concomitant deprotonation of Glu104. Water displaces the product(s) from the active site.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Cytidine deaminase Mouse
Cytidine deaminase 3 Mouse-ear cress
Cytidine deaminase 2 Mouse-ear cress
Cytidine deaminase 8 Mouse-ear cress
Putative cytidine deaminase Fission yeast