General Information of Drug-Metabolizing Enzyme (DME) (ID: DEDPI65)

DME Name Oxygen-insensitive NADPH nitroreductase A (nfsA)
Synonyms Oxygen-insensitive NAD(P)H nitroreductase A; Modulator of drug activity A; JW0835; b0851; mda18; mdaA; nfsA; pnrA; ybjB
Gene Name nfsA
UniProt ID
NFSA_ECOLI
INTEDE ID
DME1098
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
945483
EC Number EC: 1.5.1.38
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.38
Lineage Species: Escherichia coli
Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli
Tissue Distribution Primarily distributed in human gut.
Sequence
MTPTIELICGHRSIRHFTDEPISEAQREAIINSARATSSSSFLQCSSIIRITDKALREEL
VTLTGGQKHVAQAAEFWVFCADFNRHLQICPDAQLGLAEQLLLGVVDTAMMAQNALIAAE
SLGLGGVYIGGLRNNIEAVTKLLKLPQHVLPLFGLCLGWPADNPDLKPRLPASILVHENS
YQPLDKGALAQYDEQLAEYYLTRGSNNRRDTWSDHIRRTIIKESRPFILDYLHKQGWATR
Function
This enzyme is major oxygen-insensitive nitroreductase in E.coli. And it catalyzes the reduction of nitroaromatic compounds using NADPH, and has a broad electron acceptor specificity. Moreover, it reduces nitrofurazone by a ping-pong bi-bi mechanism possibly to generate a two-electron transfer product.
KEGG Pathway
Microbial metabolism in diverse environments (ecj01120 )
Nitrotoluene degradation (ecj00633 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
3 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Loperamide DMOJZQ9 Diarrhea ME05.1 Approved [1]
Nitrazepam DMEGIQ6 Epilepsy 8A60-8A68 Approved [2]
Nitrofurazone DMSM2KE Skin burns ME65.0 Approved [2]
1 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
HSDB-674 DMJG4WR N. A. N. A. Phase 1 [3]
1 Discontinued Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
CB1954 DMVP4YK Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [4]

References

1 Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans. Drug Metab Dispos. 1995 Mar;23(3):354-62.
2 Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase. J Bacteriol. 1996 Aug;178(15):4508-14.
3 Absorption of (-)-nicotine-l-N-oxide in man and its reduction in the gastrointestinal tract. J Pharm Pharmacol. 1970 Sep;22(9):722-3.
4 Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954. Biochem Pharmacol. 2010 Mar 1;79(5):678-87.