Nitroreductase: Difference between revisions

Latest revision as of 09:09, 17 July 2024

spinqualitylabelsall models

E. coli nitroreductase dimer containing FMN and nicotinic acid (PDB entry 1icr)

Drag the structure with the mouse to rotate

Export Animated Image Print3D

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 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
↑ 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
↑ 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
↑ 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

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[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:https://dx.doi.org/10.1042/BJ20150650

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-{{STRUCTURE_1icu|  PDB=1icu  | SIZE=400| SCENE= |right|CAPTION=E. coli nitroreductase containing FMN complex with nicotinic acid, [[1icu]] }}
+<StructureSection load='' size='350' side='right' caption='E. coli nitroreductase dimer containing FMN and nicotinic acid (PDB entry [[1icr]])' scene='48/489319/Cv/1'>
-<!--
+== Function ==
-Please use the "3D" button above this box to insert a Jmol applet (molecule) on this page.
+'''Nitroreductase''' or '''oxygen-insensitive NAD(P)H nitroreductase''' (NR) is involved in the reduction of nitrogen-containing compounds including those containing NO<sub>2</sub> group. The NO<sub>2</sub> group is reduced to hydroxylamine<ref>PMID:11491290</ref>.   NR uses FMN as cofactor.  Among NRs are the oxygen-insensitive NAD(P)H NR and NADH dehydrogenase.
-Or use the four-green-boxes-button to insert scrollable text adjacent
+*'''Copper-induced nitroreductase''' protects ''Lactococcus lactis'' against oxidative stress exerted by nitroaromatic compounds and copper<ref>PMID:20562311</ref>.
-to a Jmol applet. Check out the other buttons as well!
+*'''Nitrobenzoate nitroreductase''' metabolises 2-nitrobenzoate to form the antioxidant 3-hydroxyanthranilate in ''Pseudomonas fluorescens''<ref>PMID:17277060</ref>.
--->
+*'''Deazaflavin-dependent nitroreductase''' catalyses the reduction of nitroimidazoles into reactive nitrogen species in ''Mycobacterium tuberculosis'' <ref>PMID:22244759</ref>.
-'''Nitroreductase''' (NR) is involved in the reduction of nitrogen-containing compounds including those containing NO<sub>2</sub> group. The NO<sub>2</sub> group is reduced to hydroxylamine.   NR use FMN as cofactor.  Among NRs are the oxygen-insensitive NAD(P)H NR and NADH dehydrogenase.  The NR is of special interest due to its potential use as activator of prodrugs in cancer therapy.
+== Relevance ==
+NR is of special interest due to its potential use as activator of prodrugs in cancer therapy<ref>PMID:26431849</ref>.
+== Structural highlights ==
+NR <scene name='48/489319/Cv/4'>cofactor FMN is bound directly to one subunit</scene> while the <scene name='48/489319/Cv/5'>ligand - nicotinic acid - interacts with both subunits</scene>. Water molecules are shown as red spheres.
 ==3D structures of nitroreductase==
+[[Nitroreductase 3D structures]]
+</StructureSection>
-[[1f5v ]], [[1oo5]] – EcNR – ''Escherichia coli''<br />
+== References ==
-[[3bm1]], [[1ds7]] – EcNR minimal<br />
+<references/>
-[[3bm2]] – EcNR minimal -FMN<br />
-[[1nec]], [[1kqd]] – EclNR – ''Enterobacter cloacae''<br />
-[[1ywq]], [[2i7h]] – NR – ''Bacillus cereus''<br />
-[[2b67]] – NR – ''Streptococcus pneumonia''<br />
-[[3ek3]], [[3hoi]] – NR – ''Bacterioides fragilis''<br />
-[[3g14]] – NR – ''Clostridium novyi''<br />
-[[3h4o]], [[3koq]] - NR – ''Clostridium difficile''<br />
-[[3gr3]] – NR – ''Bartonella henselae''<br />
-[[3hzn]] – NR – ''Salmonella typhimurium''<br />
-[[3k6h]] – NR – ''Agrobacterium tumefaciens''<br />
-[[2wqf]] – NR – ''Lactococcus lactis''<br />
-[[2wzv]] – MsNR – ''Mycobacterium smegmatis''<br />
-[[3of4]] – NR FMN/FAD – ''Idiomarina loihiensis''<br />
-[[3n2s]] – NR – ''Bacillus subtilis''<br />
-[[3pxv]] – NR – ''Desulfitobacterium hafniense''<br />
-[[3qdl]] – NR – ''Helicobacter pylori''<br />
-[[3r5l]], [[3r5p]] - MtNR – ''Mycobacterium tuberculosis''<br />
-[[3r5r]], [[3r5w]] – MtNR F420
-'''Nitroreductase binary complex'''
-[[1kqb]] – EclNR + benzoate<br />
-[[1kqc]] – EclNR + acetate<br />
-[[1ylr]], [[1ylu]] - EcNR + acetate<br />
-[[1icr]], [[1icu]], [[1icv]] – EcNR + nicotinic acid<br />
-[[1ooq]] – EcNR + dicoumarol<br />
-[[1oo6]], [[1oon]], [[1idt]] – EcNR + benzamide derivative<br />
-[[1yki]] – EcNR + antibiotic<br />
-[[2wzw]] - MsNR + NADPH
 [[Category:Topic Page]]

Nitroreductase: Difference between revisions

Latest revision as of 09:09, 17 July 2024

Contents

Function

Relevance

Structural highlights

3D structures of nitroreductase

References

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools