J Biol Inorg Chem. 2014 Aug;19(6):893-902.

The class Ib ribonucleotide reductase from Mycobacterium tuberculosis has two active R2F subunits.

Hammerstad M, Røhr AK, Andersen NH, Gräslund A, Högbom M, Andersson KK.

Department of Biosciences, Section of Biochemistry and Molecular Biology, University of Oslo, PO Box 1066, Blindern, 0316, Oslo, Norway.



Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to their corresponding deoxyribonucleotides, playing a crucial role in DNA repair and replication in all living organisms. Class Ib RNRs require either a diiron-tyrosyl radical (Y·) or a dimanganese-Y· cofactor in their R2F subunit to initiate ribonucleotide reduction in the R1 subunit. Mycobacterium tuberculosis, the causative agent of tuberculosis, contains two genes, nrdF1 and nrdF2, encoding the small subunits R2F-1 and R2F-2, respectively, where the latter has been thought to serve as the only active small subunit in the M. tuberculosis class Ib RNR. Here, we present evidence for the presence of an active Fe 2 (III) -Y· cofactor in the M. tuberculosis RNR R2F-1 small subunit, supported and characterized by UV-vis, X-band electron paramagnetic resonance, and resonance Raman spectroscopy, showing features similar to those for the M. tuberculosis R2F-2-Fe 2 (III) -Y· cofactor. We also report enzymatic activity of Fe 2 (III) -R2F-1 when assayed with R1, and suggest that the active M. tuberculosis class Ib RNR can use two different small subunits, R2F-1 and R2F-2, with similar activity.

PMID: 24585102


This paper is one of series on ribonucleotide reductase:

  1. Hammerstad M., H.-P. Hersleth, A.B.Tomter, Å.K. Røhr and K.K. Andersson (2014) Crystal Structure of Bacillus cereus Class Ib Ribonucleotide Reductase Di-iron NrdF in Complex with NrdI. ACS Chem. Biol. 9 (2), 526-537, DOI: 10.1021/cb400757h PMID: 24295378
  2. Røhr Å.K., M. Hammerstad and K.K. Andersson (2013) Stabilization of two nucleophilic cysteines thiolates in the active site of the BC3987 thioredoxin. PLoS ONE. 8(7): e69411, DOI: 10.1371/journal.pone.0069411 PMID: 24295378
  3. Tomter, A.B., G. Zoppellaro, N.H. Andersen, H.-P. Hersleth, M. Hammerstad, Å.K. Røhr, G.K. Sandvik, K.R. Strand, G.E. Nilsson, C.B. Bell III, A.-L. Barra, E. Blasco, L. Le Pape, E.I. Solomon, and K.K. Andersson (2013) Ribonucleotide reductase class I with different radical generating clusters. Coord. Chem. Rev. 257, 3-26 DOI: 10.1016/j.ccr.2012.05.021
  4. Sandvik G.K., A.B.Tomter, J. Bergan, G. Zoppellaro, A.-L. Barra, Å.K. Røhr, M. Kolberg, S. Ellefsen, K.K. Andersson, and G.E. Nilsson (2012) Studies of Ribonucleotide Reductase in Crucian Carp – An Oxygen Dependent Enzyme in an Anoxia Tolerant Vertebrate. PloS ONE, 8 (7) e42784, 13 pages, DOI: 10.1371/journal.pone.0042784
  5. Tomter, A.B., G. Zoppellaro, C.B. Bell III, A.-L. Barra, N.H. Andersen, E.I. Solomon, and K.K. Andersson (2012) Spectroscopic Studies of the Iron- and Manganese Reconstituted Tyrosyl Radical in Bacillus cereus Ribonucleotide Reductase R2 Protein. PloS ONE 7 (3), e33436, 11 pages, DOI: 10.1371/journal.pone.0033436
  6. Tomter, A.B, G. Zoppellaro, F. Schmitzberger, N.H. Andersen, A.-L. Barra, H. Engman, P. Nordlund, and K.K. Andersson (2011) HF-EPR, Raman, UV/VIS Light Spectroscopic and DFT Studies of the Ribonucleotide Reductase R2 Tyrosyl Radical from Epstein-BarrVirus. PloS ONE, 6 (9), e25022, 11 pages, DOI: 10.1371/journal.pone.0025022


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