Nitroreductase

From Proteopedia

spinqualitylabelsall models E. coli nitroreductase dimer containing FMN and nicotinic acid (PDB entry 1icr) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Structural highlights 4 3D structures of nitroreductase 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]. Nitrobenzoate nitroreductase metabolises 2-nitrobenzoate to form the antioxidant 3-hydroxyanthranilate in Pseudomonas fluorescens[3]. Deazaflavin-dependent nitroreductase catalyses the reduction of nitroimidazoles into reactive nitrogen species in Mycobacterium tuberculosis [4]. Relevance NR is of special interest due to its potential use as activator of prodrugs in cancer therapy[5]. Structural highlights NR while the . Water molecules are shown as red spheres. 3D structures of nitroreductase Nitroreductase 3D structures

References

1. ↑ 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
2. ↑ 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
3. ↑ Iwaki H, Muraki T, Ishihara S, Hasegawa Y, Rankin KN, Sulea T, Boyd J, Lau PC. Characterization of a pseudomonad 2-nitrobenzoate nitroreductase and its catabolic pathway-associated 2-hydroxylaminobenzoate mutase and a chemoreceptor involved in 2-nitrobenzoate chemotaxis. J Bacteriol. 2007 May;189(9):3502-14. PMID:17277060 doi:10.1128/JB.01098-06
4. ↑ Cellitti SE, Shaffer J, Jones DH, Mukherjee T, Gurumurthy M, Bursulaya B, Boshoff HI, Choi I, Nayyar A, Lee YS, Cherian J, Niyomrattanakit P, Dick T, Manjunatha UH, Barry CE 3rd, Spraggon G, Geierstanger BH. Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824. Structure. 2012 Jan 11;20(1):101-12. PMID:22244759 doi:10.1016/j.str.2011.11.001
5. ↑ 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:http://dx.doi.org/10.1042/BJ20150650