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Role of the tautomerism of 2-azaadenine and 2-azahypoxanthine in substrate recognition by xanthine oxidase

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Abstract

The tautomerism of 2-azaadenine and 2-hypoxanthine has been examined in the gas phase and in aqueous solution. The tautomerism in the gas phase has been studied by means of semiempirical and ab initio quantum-mechanical computations, as well as density-functional calculations. The influence of the aqueous solvent on the relative stability between tautomers has been estimated from self-consistent reaction field calculations performed with different high-level continuum models. The results provide a detailed picture of the tautomeric preference for these purine bases. The importance of tautomerism in the substrate recognition by xanthine oxidase is discussed. Finally, the rate of oxidation of 2-azaadenine and 2- hypoxanthine by xanthine oxidase is discussed in terms of the recognition model at the enzyme active site.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Martí i Franquès 1, E-08028, Barcelona, Spain

    Begoña Hernández & Modesto Orozco

  2. Department of Pharmacy, Section Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Avinguda Diagonal s/n, E-08028, Barcelona, Spain

    Francisco J. Luque

Authors
  1. Begoña Hernández
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  2. Modesto Orozco
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  3. Francisco J. Luque
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Hernández, B., Orozco, M. & Luque, F.J. Role of the tautomerism of 2-azaadenine and 2-azahypoxanthine in substrate recognition by xanthine oxidase. J Comput Aided Mol Des 11, 153–162 (1997). https://doi.org/10.1023/A:1008082425628

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