Ile209 of Leishmania donovani xanthine phosphoribosyltransferase plays a key role in determining its purine base specificity

Xanthine phosphoribosyltransferase (XPRT) and hypoxanthine-guanine (HGPRT) are purine salvaging enzymes of Leishmania donovani with distinct 6-oxopurine specificities. LdXPRT phosphoribosylates xanthine, hypoxanthine, guanine, preference toward whereas LdHGPRT only hypoxanthine guanine. In our study, was used as a model to understand these base Mutating I209 V, the conserved residue found in HGPRTs, reduced affinity for converting it an HGXPRT-like enzyme. The Y208F mutation active site indicated that aromatic interactions ring limited pi-pi binding forces do not impart specificity. Deleting unique motif (L55-Y82) affected enzyme activity. Our studies established key determining specificity LdXPRT.