Reactivity studies of the tyrosyl radical in ribonucleotide reductase fromMycobacterium tuberculosis and Arabidopsis thaliana - Comparison with Escherichia coli and mouse

Ribonucleotide reductase (RNR) is a key enzyme for DNA synthesis since it p rovides cells with deoxyribonucleotides, the DNA precursors. Class I alpha 2 beta 2 RNRs contain a dinuclear iron center and an essential tyrosyl radi cal in the beta 2 component (protein R2). This is also true for the purifie d protein R2 of Mycobacterium tuberculosis RNR, as shown by iron analysis, light absorption and EPR spectroscopy. EPR spectroscopy at 286 GHz revealed a high g(x) value, suggesting that the radical is not hydrogen bonded, as in other prokaryotic R2s and in contrast with eukaryotic R2s (from Arabidop sis thaliana and mouse). Furthermore, it proved to be very resistant to sca venging by a variety of phenols and thiols and by hydroxyurea, similar to t he Escherichia coli radical. By comparison, the plant and mouse radicals ar e very sensitive to drugs such as resveratrol and 2-thiophenthiol. The radi cal from M. tuberculosis RNR does not seem to be an appropriate target for new antituberculous agents