Identification of an immunodominant Babesia gibsoni 47-kDa antigen
Aboge, G O
Terkawi, M A
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The inosine monophosphate dehydrogenase(IMPDH )enzyme has been characterized and validate dasa molecular drug target in other apicomplexans butnot in the genus Babesia. Subsequently,we cloned and expressed a Babesia gibsoniIMPDH (BgIMPDH) cDNA in Escherichia coli.We also determined the inhibitory effect of mycophenolic acid (MPA) on recombinant BgIMPDH (rBgIMPDH) activity and the Babesia-growths in vitro. The translated BgIMPDH peptide contained thirteen amino acid residues responsible for substrate and cofactor binding in its catalytic domain with Gly374 in BgIMPDH being replaced by Ser388 in mammalian IMPDH. The native BgIMPDH enzyme in the parasite was approximately 54-k Daa mass similar to His-tagrBgIMPDH protein.The Km values of ther Bg IMPDH were 8.18±0.878 (mean±standard error of the mean)μM and 360.80±43.41μM forIMPandNAD+,respectively.MPA inhibited the rBgIMPDH activity yielding a Ki value of 20.93±1.83μMwithrespecttoNAD+.For Babesia growths, the IC50s were 0.95±0.21 and 2.88±0.49μMforB. gibsoni and B. bovis, respectively. Therefore, our results suggest that MPA may inhibit there placation of Babesia parasites by targeting IMPDH enzyme of the purine pathway.