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Overview
Mycobacterium tuberculosis resides in the lungs of a host and upon becoming active, results in symptoms such as chest pains, weakness, and intense coughing. Left untreated and unmanaged, TB can lead to death (1.5 million in 2013). The disease has a high co-morbidity with HIV/AIDS due to its immunocompromising tendencies. Tuberculosis is one of the most heavily studied diseases today. With over 9 million infections worldwide per year, the necessity for antimicrobial agents to combat emerging multi-drug resistant strands is imperative. Mycobacterium tuberculosis NrdH is a small glutaredoxin-like protein involved in the electron transport chain that eventually leads to ribonucleotide reduction in tuberculosis.
Background
MtNrdH has been identified as an electron carrier protein in ribonuleotide reduction. Ribonucleotide reduction uses an enzyme called ribonucleotide reductase (RNR) to make deoxyribonucleotides, which act as precursors to DNA synthesis. Three classes of RNRs have been identified; each class differs in cofactor requirement, structure, and oxygen dependence, but the general catalytic mechanism is conserved in all three classes. Mycobacterium tuberculosis uses class I ribonucleotide reductase.
Class 1 RNR is further subdivided into class Ia and Ib. Both Ia and Ib reduce ribonucleotide 5’ diphosphate to deoxyribonucleotide 5’ diphosphate (NDP dNDP). After ribonucleotide reductase performs the first round of reduction, RNR must be reduced again to reset the cycle. In class Ib, RNR is reduced by either glutadoxin or thiordoxin, which are first reduced by glutadoxin reductase and thiordoxin reductase, respectively. In class Ib, RNR is reduced by NrdE, which is first reduced by NrdH. An important distinction between Ia and Ib is that Ia is present in eukaryotes, eubacteria, bacteriophages, and virus, but Ib is only present in eubacteria.
Function
Disease
Relevance
Structural highlights
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
