Research progress: Low stability of the reduced state of Mycobacterium tuberculosis NrdH redoxin

[2016.1.20] We published a paper on FEBS Letters: Low stability of the reduced state of Mycobacterium tuberculosis NrdH redoxin. NrdH redoxin is the only hydrogen donor for ribonucleotide reductase in Mycobacterium tuberculosis. Several crystal structures of NrdH redoxins in the oxidized state from different species have been reported, but no structure of the reduced state has yet been reported. We characrized the oxidized and reduced states of NrdH redoxin from M. tuberculosis (MtNrdH) and found that MtNrdH is largely unfolded at a pH lower than the pKa of its first active-site cysteine, and the structural basis of the low stability was analyzed. In addition, a single mutant of the NrdH redoxin suitable to determine the structure in the reduced state was obtained. The poor stability of MtNrdH makes it a good drug target, and the pH dependence of the stability provides a possible strategy for tuberculosis treatment. Our mutagenesis results also make the structural determination of the reduced state possible, which may provide further clues for drug development targeting the essential NrdH redoxin of M. tuberculosis.

Associate Prof. Dr. Ya-Jun Liu in our group is the first author. The research was supervised by Prof. Yingang Feng, and was financially supported by the National Natural Science Foundation of China.

NCBI PubMed 

Ya-Jun Liu, Xiaxia Song, Yifei Li, Jinsong Xuan, Qiu Cui, Jinfeng Wang, Yingang Feng* (2016) Low stability of the reduced state of Mycobacterium tuberculosis NrdH redoxin. FEBS Lett. In press.[PMID:26786191 ] [Full text (Publisher website)]