Dihydrofolate Reductase from Eimeria tenella: Rationalization of Chemotherapeutic Efficacy of Pyrimethamine |
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Authors: | CHING CHUNG WANG RONALD L STOTISH MARTIN POE |
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Institution: | Merck Institute for Therapeutic Research, Railway, New Jersey 07065 |
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Abstract: | SYNOPSIS. Dihydrofolate reductase activity of 0.2 nmole of dihydrofolate reduced/min/mg protein was detected in crude extracts of unsporulated oocysts of Eimeria tenella. The enzyme was purified by a combination of affinity and ion-exchange chromatography. Its molecular weight was estimated as 240,000 daltons. An anticoccidial drug pyrimethamine is a potent inhibitor of the activity of E. tenella dihydrofolate reductase ( K t = 3 nM), but it is less effective an inhibitor of dihydrofolate reductase from chicken liver. This difference may explain the in vivo therapeutic action of pyrimethamine against Coccidia. |
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Keywords: | Eimeria tenella dihydrofolate reductase from chicken liver pyrimethamine |
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