Interaction with Glycine Increases Stability of Mutagenic Tautomer of Uracil. A Density Functional Theory Study.

The most stable structures for the gas-phase complexes of minor tautomers of uracil (U) with glycine (G) were characterized at the density functional B3LYP/6-31 ++G** level of theory. These are cyclic structures stabilized by two hydrogen bonds. The relative stability of isolated tautomers of uracil...

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Publicado en:Journal of the American Chemical Society Vol. 127; no. 7; pp. 2238 - 2249
Autores principales: D&acedil;bkowska, Iwona, Gutowski, Maciej, Rak, Janusz
Formato: Artículo
Publicado: American Chemical Society 2/23/2005
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2/23/2005
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        10.1021/ja048730k
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        atl: Interaction with Glycine Increases Stability of Mutagenic Tautomer of Uracil. A Density Functional Theory Study.
      aug:
        au:
          D&acedil;bkowska, Iwona
          Gutowski, Maciej
          Rak, Janusz
        affil:
          Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland
          Chemical Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352
      su:
        Density functionals
        Glycine
        Amino acid neurotransmitters
        Mutagens
        Tautomerism
        Uracil
        Thermodynamics
      sug:
        subj:
          Density functionals
          Glycine
          Amino acid neurotransmitters
          Mutagens
          Tautomerism
          Uracil
          Thermodynamics
      ab: The most stable structures for the gas-phase complexes of minor tautomers of uracil (U) with glycine (G) were characterized at the density functional B3LYP/6-31 ++G** level of theory. These are cyclic structures stabilized by two hydrogen bonds. The relative stability of isolated tautomers of uracil was rationalized by using thermodynamic and structural arguments. The stabilization energies for complexes between the tautomers of U and G result from interplay between the stabilizing two-body interaction energies and destabilizing one-body terms. The latter are related to the energies of (i) tautomerization of the unperturbed moieties and (ii) distortions of the resulting rare tautomers in the complex. The two-body term describes the interaction energy between distorted tautomers. The two-body interaction energy term correlates with perturbations of length of the proton-donor bonds as well as with deprotonation enthalpies and proton affinities of the appropriate monomer sites. It was demonstrated that the relative instability of rare tautomers of uracil is diminished due to their interactions with glycine. In particular, the instability of the third most stable tautomer (U) is decreased from 11.9 kcal/mol for non-interacting uracil to 6.7 kcal/mol for uracil in a complex with the zwitterionic tautomer of glycine. A decrease of Instability by 5.2 kcal/mol could result in an increase of concentration of U by almost 5 orders of magnitude. This is the tautomer with proton donor and acceptor sites matching guanine rather than adenine. Moreover, kinetic characteristics obtained for the glycine-assisted conversion of the most stable tautomer of uracll (U) to U indicate that the U↔U thermodynamic equilibrium could be easily attained at room temperature. The resulting concentration of this tautomer falls in a mutationally significant range.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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