Trypanothione-dependent Synthesis of Deoxyribonucleotides byTrypanosoma bruceiRibonucleotide Reductase

摘要: Abstract Trypanosoma brucei, the causative agent of African sleeping sickness, synthesizes deoxyribonucleotides via a classical eukaryotic class I ribonucleotide reductase. The unique thiol metabolism trypanosomatids in which nearly ubiquitous glutathione reductase is replaced by trypanothione prompted us to study nature thiols providing reducing equivalents for parasite synthesis DNA precursors. Here we show that dithiol (bis(glutathionyl)spermidine), contrast glutathione, direct reductant T. bruceiribonucleotide with K m value 2 mm. This first example natural low molecular mass directly delivering reduction. At submillimolar concentrations, reaction strongly accelerated tryparedoxin, 16-kDa protein WCPPC active site motif. brucei bruceitryparedoxin about 4 μm. disulfide form powerful inhibitor tryparedoxin-mediated may represent physiological regulation deoxyribonucleotide redox state cell. trypanothione/tryparedoxin system new electrons reductase, addition well known thioredoxin and glutaredoxin systems described other organisms.