{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:57:28Z","timestamp":1769216248168,"version":"3.49.0"},"reference-count":52,"publisher":"Cambridge University Press (CUP)","issue":"6","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>There is an alarming rate of human African trypanosomiasis recrudescence in many parts of sub-Saharan Africa. Yet, the disease has no successful chemotherapy.<jats:italic>Trypanosoma<\/jats:italic>lacks the enzymatic machinery for the<jats:italic>de novo<\/jats:italic>synthesis of purine nucleotides, and is critically dependent on salvage mechanisms. Inosine 5\u2032-monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide metabolism. Here, we characterize recombinant<jats:italic>Trypanosoma brucei<\/jats:italic>IMPDH (TbIMPDH) to investigate the enzymatic differences between TbIMPDH and host IMPDH. Size-exclusion chromatography and analytical ultracentrifugation sedimentation velocity experiments reveal that TbIMPDH forms a heptamer, different from type 1 and 2 mammalian tetrameric IMPDHs. Kinetic analysis reveals calculated<jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub>values of 30 and 1300\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>for IMP and NAD, respectively. The obtained<jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub>value of TbIMPDH for NAD is approximately 20\u2013200-fold higher than that of mammalian enzymes and indicative of a different NAD binding mode between trypanosomal and mammalian IMPDHs. Inhibition studies show<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>values of 3\u00b72\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>, 21 nM and 3\u00b73 nM for ribavirin 5\u2032-monophosphate, mycophenolic acid and mizoribine 5\u2032-monophosphate, respectively. Our results show that TbIMPDH is different from its mammalian counterpart and thus may be a good target for further studies on anti-trypanosomal drugs.<\/jats:p>","DOI":"10.1017\/s0031182012002090","type":"journal-article","created":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T16:49:44Z","timestamp":1359737384000},"page":"735-745","source":"Crossref","is-referenced-by-count":14,"title":["Characterization of the novel<i>Trypanosoma brucei<\/i>inosine 5\u2032-monophosphate 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