Screening of substrate analogs as potential enzyme inhibitors for the arginine kinase of Trypanosoma cruzi.

PEREIRA, CLAUDIO; ALONSO, GUILLERMO; IVALDI, SOLEDAD; BOUVIER, LEÓN ALBERTO; TORRES, HECTOR; FLAWIA, MIRTHA

JOURNAL OF EUKARYOTIC MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2003 vol. 50 p. 132 - 134

1066-5234

Arginine kinase catalyzes the transphosphorylation between phosphoarginine and ADP. Phosphoarginine is involved in temporal ATP buffering and inorganic phosphate regulation. Trypanosoma cruzi arginine kinase phosphorylates only L-arginine (specific activity 398.9 x mUE-min(-1) x mg(-1)), and is inhibited by the arginine analogs, agmatine, canavanine, nitroarginine, and homoarginine. Canavanine and homoarginine also produce a significant inhibition of the epimastigote culture growth (79.7% and 55.8%, respectively). Inhibition constants were calculated for canavanine and homoarginine (7.55 and 6.02 mM, respectively). In addition, two novel guanidino kinase activities were detected in the epimastigote soluble extract. The development of the arginine kinase inhibitors of T. cruzi could be an important feature because the phosphagens biosynthetic pathway in trypanosomatids is different from the one in their mammalian hosts.