Journal of Computer-Aided Molecular Design 1997-03-01

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

B Hernández, M Orozco, F J Luque

Index: J. Comput. Aided Mol. Des. 11(2) , 153-62, (1997)

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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.