JBIC Journal of Biological Inorganic Chemistry

, Volume 12, Issue 8, pp 1119–1127

Genomic analysis reveals widespread occurrence of new classes of copper nitrite reductases

  • Mark J. Ellis
  • J. Günter Grossmann
  • Robert R. Eady
  • S. Samar Hasnain
Original Paper

DOI: 10.1007/s00775-007-0282-2

Cite this article as:
Ellis, M.J., Grossmann, J.G., Eady, R.R. et al. J Biol Inorg Chem (2007) 12: 1119. doi:10.1007/s00775-007-0282-2


Recently, the structure of a Cu-containing nitrite reductase (NiR) from Hyphomicrobium denitrificans (HdNiR) has been reported, establishing the existence of a new family of Cu-NiR where an additional type 1 Cu (T1Cu) containing cupredoxin domain is located at the N-terminus (Nojiri et al. in Proc. Natl. Acad. Sci. USA 104:4315–4320, 2007). HdNiR retains the well-characterised coupled T1Cu–type 2 Cu (T2Cu) core, where the T2Cu catalytic site is also built utilising ligands from neighbouring monomers. We have undertaken a genome analysis and found the wide occurrence of these NiRs, with members clustering in two groups, one showing an amino acid sequence similarity of around 80% with HdNiR, and a second group, including the NiR from the extremophile Acidothermus cellulolyticus, clustering around 50% similarity to HdNiR. This is reminiscent of the difference observed between the blue (Alcaligenes xylosoxidans) and green (Achromobacter cycloclastes and Alcaligenes faecalis) NiRs which have been extensively studied and may indicate that these also form two distinct subclasses of the new family. Genome analysis also showed the presence of Cu-NiRs with a C-terminal extension of 160–190 residues containing a class I cytochrome c domain with a characteristic β-sheet extension. Currently no structural information exists for any member of this family. Genome analysis suggests the widespread occurrence of these novel NiRs with representatives in the α, β and γ subclasses of the Proteobacteria and in two species of the fungus Aspergillus. We selected the enzyme from Ralstonia pickettii for comparative modelling and produced a plausible structure highlighting an electron transfer mode in which the cytochrome c haem at the C-terminus can come within 16-Å reach of the T1Cu centre of the T1Cu–T2Cu core.


Nitrite reductasec-type cytochromeBlue copper proteinElectron transfer



Acidothermus cellulolyticus nitrite reductase


Achromobacter cycloclastes nitrite reductase


Alcaligenes faecalis S6 nitrite reductase


Alcaligenes xylosoxidans nitrite reductase


Bdellovibrio bacteriovorus nitrite reductase


Blue copper protein


Chaetomium globosum nitrite reductase


Chromobacterium violaceum nitrite reductase


Hyphomicrobium denitrificans nitrite reductase


Neisseria gonorrhoeae nitrite reductase


Nitrite reductase


Protein Homology/analogY Recognition Engine


Ralstonia pickettii 12J nitrite reductase


Type 1 copper


Type 2 copper

Supplementary material

Copyright information

© SBIC 2007

Authors and Affiliations

  • Mark J. Ellis
    • 1
  • J. Günter Grossmann
    • 1
  • Robert R. Eady
    • 1
  • S. Samar Hasnain
    • 1
  1. 1.Molecular Biophysics Group, Science and Technology Facilities CouncilDaresbury LaboratoryWarringtonUK