The deamination of cytidine performed by cytidine deaminase has been modeled using density functional theory yielding a reaction mechanism differing from that previously reported using semiempirical results. The main difference consists in the initial reaction step starting with Zn-bound water and N3-protonated cytidine. This study allows for the first time to close complete reaction cycle for the investigated process. (C) 2003 Elsevier B.V. All rights reserved.