Proton catalyzed hydrolytic deamination of cytosine: a computational study

Vanessa Labet 1 André Grand 1 Christophe Morell 1 Jean Cadet 1 Leif A. Eriksson 2
1 LAN - Laboratoire Lésions des Acides Nucléiques
SCIB - UMR E3 - Service de Chimie Inorganique et Biologique : DSM/INAC/SCIB
Abstract : Two pathways involving proton catalyzed hydr-olytic deamination of cytosine (to uracil) are investigated at the PCM-corrected B3LYP/6-311G(d,p) level of theory, in the presence of an additional catalyzing water molecule. It is concluded that the pathway involving initial protonation at nitrogen in position 3 of the ring, followed by water addition at C4 and proton transfer to the amino group, is a likely route to hydrolytic deamination. The rate determining step is the addition of water to the cytosine, with a calculated free energy barrier in aqueous solution of G = =140 kJ/mol. The current mechanism provides a lower barrier to deamina-tion than previous work based on OH − catalyzed reactions, and lies closer to the experimental barrier derived from rate constants (E a = 117 ± 4 kJ/mol). Keywords Cytosine · Hydrolytic deamination · B3LYP · Mutation · DNA Dedicated to Professor Nino Russo on the occasion of his 60th birthday. Electronic supplementary material The online version of this article (
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Vanessa Labet, André Grand, Christophe Morell, Jean Cadet, Leif A. Eriksson. Proton catalyzed hydrolytic deamination of cytosine: a computational study. Theoretical Chemistry Accounts: Theory, Computation, and Modeling, Springer Verlag, 2008, 120 (4-6), pp.429-435. ⟨10.1007/s00214-008-0418-7⟩. ⟨hal-02202079⟩

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