Role of tautomerism of 2-azaadenine and 2-azahypoxanthine in substrate recognition by xanthine oxidase.
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.
Hernández
B
B
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Spain.
Orozco
M
M
Luque
F J
FJ
D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D001665:Binding Sites; D005740:Gases; D007042:Hypoxanthines / Q000737:chemistry*; D066298:In Vitro Techniques; D007536:Isomerism; D008958:Models, Molecular; D015394:Molecular Structure; D012996:Solutions; D013379:Substrate Specificity; D013816:Thermodynamics; D014867:Water; D014969:Xanthine Oxidase / Q000737:chemistry / Q000378:metabolism*
D005740:Gases; D007042:Hypoxanthines; D012996:Solutions; D014867:Water; C073377:2-azaadenine; D014969:Xanthine Oxidase; D000225:Adenine; C012759:2-azahypoxanthine