In:
FEBS Letters, Wiley, Vol. 595, No. 16 ( 2021-08), p. 2169-2182
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1002/feb2.v595.16
DOI:
10.1002/1873-3468.14162
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
1460391-3
SSG:
12
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