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

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Bhumi Patel¹  Dhaval Patel¹  Anju Pappachan¹ 

[1] Indian Institute of Advanced Research ,(Puri Foundation for Education in India), Koba Institutional Area;School of Life Sciences, Central University of Gujarat

关键词: guanine;    hypoxanthine;    Leishmania;    phosphoribosyltransferases;    purine salvage;    purine specificity;    xanthine;    xanthine phosphoribosyltransferase;   

DOI  :  10.1002/1873-3468.14162

来源: John Wiley & Sons Ltd.

【 摘 要 】

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

【 授权许可】

Unknown