Function
Nitroreductase or oxygen-insensitive NAD(P)H nitroreductase (NR) is involved in the reduction of nitrogen-containing compounds including those containing NO2 group. The NO2 group is reduced to hydroxylamine[1]. NR uses FMN as cofactor. Among NRs are the oxygen-insensitive NAD(P)H NR and NADH dehydrogenase.
- Copper-induced nitroreductase protects Lactococcus lactis against oxidative stress exerted by nitroaromatic compounds and copper[2].
Relevance
NR is of special interest due to its potential use as activator of prodrugs in cancer therapy[3].
Structural highlights
NR cofactor FMN is bound directly to one subunit while the ligand - nicotinic acid - interacts with both subunits. Water molecules are shown as red spheres.
3D structures of nitroreductase
Nitroreductase 3D structures
- ↑ Lovering AL, Hyde EI, Searle PF, White SA. The structure of Escherichia coli nitroreductase complexed with nicotinic acid: three crystal forms at 1.7 A, 1.8 A and 2.4 A resolution. J Mol Biol. 2001 May 25;309(1):203-13. PMID:11491290 doi:10.1006/jmbi.2001.4653
- ↑ Mermod M, Mourlane F, Waltersperger S, Oberholzer AE, Baumann U, Solioz M. Structure and function of CinD (YtjD) of Lactococcus lactis, a copper-induced nitroreductase involved in defense against oxidative stress. J Bacteriol. 2010 Aug;192(16):4172-80. Epub 2010 Jun 18. PMID:20562311 doi:10.1128/JB.00372-10
- ↑ Williams EM, Little RF, Mowday AM, Rich MH, Chan-Hyams JV, Copp JN, Smaill JB, Patterson AV, Ackerley DF. Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility. Biochem J. 2015 Oct 15;471(2):131-53. doi: 10.1042/BJ20150650. PMID:26431849 doi:https://dx.doi.org/10.1042/BJ20150650