Thymidine kinase and uridine-cytidine kinase from Entamoeba histolytica: Cloning, characterization, and search for specific inhibitors

A. Lossani, A. Torti, S. Gatti, A. Bruno, R. Maserati, G. E. Wright, F. Focher

Research output: Contribution to journalArticlepeer-review

Abstract

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Although anti-amoebic drugs such as metronidazole, emetine, chloroquine and nitazoxanide are generally effective, there is always potential for development of drug resistance. In order to find novel targets to control E. histolytica proliferation we cloned, expressed and purified thymidine kinase (Eh-TK) and uridine-cytidine kinase (Eh-UCK) from E. histolytica. Eh-TK phosphorylates thymidine with a Km of 0.27 μm, whereas Eh-UCK phosphorylates uridine and cytidine with Km of 0.74 and 0.22 mm, respectively. For both enzymes, ATP acts as specific phosphate donor. In order to find alternative treatments of E. histolytica infection we tested numerous nucleoside analogues and related compounds as inhibitors and/or substrates of Eh-TK and Eh-UCK, and active compounds against E. histolytica in cell culture. Our results indicate that inhibitors or alternative substrates of the enzymes, although partially reducing protozoan proliferation, are reversible and not likely to become drugs against E. histolytica infections.

Original languageEnglish
Pages (from-to)595-602
Number of pages8
JournalParasitology
Volume136
Issue number6
DOIs
Publication statusPublished - May 2009

Keywords

  • Amoebiasis
  • Drugs
  • Entamoeba
  • Inhibitors
  • Kinases

ASJC Scopus subject areas

  • Parasitology
  • Animal Science and Zoology
  • Infectious Diseases

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