Oxygen-insensitive NAD(P)H nitroreductase (P38489)

Identification
Name:Oxygen-insensitive NAD(P)H nitroreductase
Synonyms:
  • Dihydropteridine reductase
  • FMN-dependent nitroreductase
Gene Name:nfnB
Enzyme Class:
Biological Properties
General Function:Involved in oxidoreductase activity
Specific Function:Reduction of a variety of nitroaromatic compounds using NADH (and to lesser extent NADPH) as source of reducing equivalents; two electrons are transferred. Capable of reducing nitrofurazone, quinones and the anti-tumor agent CB1954 (5- (aziridin-1-yl)-2,4-dinitrobenzamide). The reduction of CB1954 results in the generation of cytotoxic species
Cellular Location:Not Available
SMPDB Pathways:
KEGG Pathways:
KEGG Reactions:
1.0Trinitrotoluene+2.0Thumb+2.0Thumb ↔ 1.04-Hydroxylamino-2,6-dinitrotoluene+2.0Thumb+1.0Thumb
1.0Trinitrotoluene + 2.0NADPH + 2.0Hydrogen ion ↔ 1.04-Hydroxylamino-2,6-dinitrotoluene + 2.0NADP + 1.0Water
ReactionCard
1.0Trinitrotoluene+2.0Thumb+2.0Thumb ↔ 1.04-Hydroxylamino-2,6-dinitrotoluene+2.0Thumb+1.0Thumb
1.0Trinitrotoluene + 2.0NADH + 2.0Hydrogen ion ↔ 1.04-Hydroxylamino-2,6-dinitrotoluene + 2.0NAD + 1.0Water
ReactionCard
1.0Trinitrotoluene+2.0Thumb+2.0Thumb ↔ 1.02-Hydroxylamino-4,6-dinitrotoluene+2.0Thumb+1.0Thumb
1.0Trinitrotoluene + 2.0NADH + 2.0Hydrogen ion ↔ 1.02-Hydroxylamino-4,6-dinitrotoluene + 2.0NAD + 1.0Water
ReactionCard
1.0Thumb+1.0Thumb+1.0Thumb ↔ 1.0Thumb+1.0Thumb+1.0Thumb+1.0Thumb
1.0Tetrahydropteridine + 1.0NAD + 1.0NADP ↔ 1.06,7-Dihydropteridine + 1.0NADH + 1.0NADPH + 1.0Hydrogen ion
ReactionCard
Complex Reactions:
1.0Thumb+3.0Thumb+1.0Thumb ↔ 1.0Thumb+1.0Thumb
1.06,7-Dihydropteridine + 3.0Hydrogen ion + 1.0NADH ↔ 1.0NAD + 1.0Tetrahydropteridine
ReactionCard
1.0Thumb+3.0Thumb+1.0Thumb ↔ 1.0Thumb+1.0Thumb
1.06,7-Dihydropteridine + 3.0Hydrogen ion + 1.0NADPH ↔ 1.0NADP + 1.0Tetrahydropteridine
ReactionCard
1.0Thumb+1.0Thumb → 1.0Thumb+1.0Thumb
1.0Tetrahydropteridine + 1.0NAD → 1.06,7-Dihydropteridine + 1.0NADH
ReactionCard
1.0Thumb+1.0Thumb → 1.0Thumb+1.0Thumb
1.0Tetrahydropteridine + 1.0NADP → 1.06,7-Dihydropteridine + 1.0NADPH
ReactionCard
Metabolites:
ECMDB IDNameView
ECMDB014416,7-DihydropteridineMetaboCard
ECMDB21225Hydrogen ionMetaboCard
ECMDB00902NADMetaboCard
ECMDB01487NADHMetaboCard
ECMDB00217NADPMetaboCard
ECMDB04111NADPHMetaboCard
ECMDB01216TetrahydropteridineMetaboCard
ECMDB00494WaterMetaboCard
GO Classification:
Function
catalytic activity
oxidoreductase activity
Gene Properties
Blattner:b0578
Gene OrientationCounterclockwise
Centisome Percentage:13.02
Left Sequence End603994
Right Sequence End604647
Gene Sequence:
>654 bp
ATGGATATCATTTCTGTCGCCTTAAAGCGTCATTCCACTAAGGCATTTGATGCCAGCAAA
AAACTTACCCCGGAACAGGCCGAGCAGATCAAAACGCTACTGCAATACAGCCCATCCAGC
ACCAACTCCCAGCCGTGGCATTTTATTGTTGCCAGCACGGAAGAAGGTAAAGCGCGTGTT
GCCAAATCCGCTGCCGGTAATTACGTGTTCAACGAGCGTAAAATGCTTGATGCCTCGCAC
GTCGTGGTGTTCTGTGCAAAAACCGCGATGGACGATGTCTGGCTGAAGCTGGTTGTTGAC
CAGGAAGATGCCGATGGCCGCTTTGCCACGCCGGAAGCGAAAGCCGCGAACGATAAAGGT
CGCAAGTTCTTCGCTGATATGCACCGTAAAGATCTGCATGATGATGCAGAGTGGATGGCA
AAACAGGTTTATCTCAACGTCGGTAACTTCCTGCTCGGCGTGGCGGCTCTGGGTCTGGAC
GCGGTACCCATCGAAGGTTTTGACGCCGCCATCCTCGATGCAGAATTTGGTCTGAAAGAG
AAAGGCTACACCAGTCTGGTGGTTGTTCCGGTAGGTCATCACAGCGTTGAAGATTTTAAC
GCTACGCTGCCGAAATCTCGTCTGCCGCAAAACATCACCTTAACCGAAGTGTAA
Protein Properties
Pfam Domain Function:
Protein Residues:217
Protein Molecular Weight:23905
Protein Theoretical pI:6
PDB File:1YLU
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Oxygen-insensitive NAD(P)H nitroreductase
MDIISVALKRHSTKAFDASKKLTPEQAEQIKTLLQYSPSSTNSQPWHFIVASTEEGKARV
AKSAAGNYVFNERKMLDASHVVVFCAKTAMDDVWLKLVVDQEDADGRFATPEAKAANDKG
RKFFADMHRKDLHDDAEWMAKQVYLNVGNFLLGVAALGLDAVPIEGFDAAILDAEFGLKE
KGYTSLVVVPVGHHSVEDFNATLPKSRLPQNITLTEV
References
External Links:
ResourceLink
Uniprot ID:P38489
Uniprot Name:NFNB_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:1651240
PDB ID:1YLU
Ecogene ID:EG20151
Ecocyc:EG20151
ColiBase:b0578
Kegg Gene:b0578
EchoBASE ID:EB4146
CCDB:NFNB_ECOLI
BacMap:16128561
General Reference:
  • Anlezark, G. M., Melton, R. G., Sherwood, R. F., Coles, B., Friedlos, F., Knox, R. J. (1992). "The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)--I. Purification and properties of a nitroreductase enzyme from Escherichia coli--a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT)." Biochem Pharmacol 44:2289-2295. Pubmed: 1472094
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Johansson, E., Parkinson, G. N., Denny, W. A., Neidle, S. (2003). "Studies on the nitroreductase prodrug-activating system. Crystal structures of complexes with the inhibitor dicoumarol and dinitrobenzamide prodrugs and of the enzyme active form." J Med Chem 46:4009-4020. Pubmed: 12954054
  • Link, A. J., Robison, K., Church, G. M. (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18:1259-1313. Pubmed: 9298646
  • Lovering, A. L., Hyde, E. I., Searle, P. F., White, S. A. (2001). "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 309:203-213. Pubmed: 11491290
  • Michael, N. P., Brehm, J. K., Anlezark, G. M., Minton, N. P. (1994). "Physical characterisation of the Escherichia coli B gene encoding nitroreductase and its over-expression in Escherichia coli K12." FEMS Microbiol Lett 124:195-202. Pubmed: 7813889
  • Oshima, T., Aiba, H., Baba, T., Fujita, K., Hayashi, K., Honjo, A., Ikemoto, K., Inada, T., Itoh, T., Kajihara, M., Kanai, K., Kashimoto, K., Kimura, S., Kitagawa, M., Makino, K., Masuda, S., Miki, T., Mizobuchi, K., Mori, H., Motomura, K., Nakamura, Y., Nashimoto, H., Nishio, Y., Saito, N., Horiuchi, T., et, a. l. .. (1996). "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map." DNA Res 3:137-155. Pubmed: 8905232
  • Parkinson, G. N., Skelly, J. V., Neidle, S. (2000). "Crystal structure of FMN-dependent nitroreductase from Escherichia coli B: a prodrug-activating enzyme." J Med Chem 43:3624-3631. Pubmed: 11020276
  • Race, P. R., Lovering, A. L., Green, R. M., Ossor, A., White, S. A., Searle, P. F., Wrighton, C. J., Hyde, E. I. (2005). "Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme." J Biol Chem 280:13256-13264. Pubmed: 15684426
  • Vasudevan, S. G., Shaw, D. C., Armarego, W. L. (1988). "Dihydropteridine reductase from Escherichia coli." Biochem J 255:581-588. Pubmed: 3060113
  • Zenno, S., Koike, H., Tanokura, M., Saigo, K. (1996). "Gene cloning, purification, and characterization of NfsB, a minor oxygen-insensitive nitroreductase from Escherichia coli, similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri." J Biochem 120:736-744. Pubmed: 8947835