Background: Nucleoside phosphorylases catalyze the reversible phosphorolysis of pyrimidine and
purine nucleosides in the presence of phosphate. They are relevant to the appropriate function of the immune
system in mammals and interesting drug targets for cancer treatment. Next to their role as drug targets nucleoside
phosphorylases are used as catalysts in the synthesis of nucleosides and their analogs that are widely applied as
Methods: Based on their substrates nucleoside phosphorylases are classified as pyrimidine and purine nucleoside
phosphorylases. This article describes the substrate spectra of nucleoside phosphorylases and structural properties
that influence their activity. Substrate ranges are summarized and relations between members of pyrimidine or
purine nucleoside phosphorylases are elucidated.
Results: Nucleoside phosphorylases accept a broad spectrum of substrates: they accept both base and sugar modified
nucleosides. The most widely studied nucleoside phosphorylases are those of Escherichia coli, mammals and
pathogens. However, recently the attention has been shifted to thermophilic nucleoside phosphorylases due to
several advantages. Nucleoside phosphorylases have been applied to produce drugs like ribavirin or fludarabine.
However, limitations were observed when drugs show an open ring structure. Site-directed mutagenesis approaches
were shown to alter the substrate specificity of nucleoside phosphorylases.
Conclusion: Nucleoside phosphorylases are valuable tools to produce modified nucleosides with therapeutic or
diagnostic potential with high affinity and specificity. A wide variety of nucleoside phosphorylases are available
in nature which differ in their protein sequence and show varying substrate spectra. To overcome limitations of
the naturally occurring enzymes site-directed mutagenesis approaches can be used.