A quantum chemical study of the catalysis for cytidine deaminase: contribution of the extra water molecule.

Cytidine deaminase is known as an important enzyme responsible for the hydrolytic deamination of cytidine, which is applied as a key step to the conversion of the precursor of the cancer drug to an active form in the living body. Cytidine with water is efficiently converted to uridine with ammonia in the cleft of cytidine deaminase. In this work, the catalysis of cytidine deaminase for the hydrolytic deamination was examined using cytosine as a model of cytidine and the model molecules for the active site of cytidine deaminase by means of the quantum chemical method. We especially investigated the contribution of the water molecule from the solvent to the catalysis, because the X-ray diffraction analysis of a crystal structure has revealed the existence of the water molecule in the vicinity of the substrate bound to the active site inside the cleft. Our computations showed that the extra water molecule from the solvent has a possibility to support the catalysis of cytidine deaminase.