Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DME1098)
DME Name Oxygen-insensitive NADPH nitroreductase A (nfsA), Escherichia coli
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
Gene ID
945483
EC Number    EC: 1.5.1.38     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.38
Lineage    Species: Escherichia coli     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli
Interactome
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       Interactions between Xenobiotics and DME (XEOTIC)                      
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       Interactions between Host Protein and DME (HOSPPI)                     
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      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Tissue Distribution Primarily distributed in human gut.
Sequence
MTPTIELICGHRSIRHFTDEPISEAQREAIINSARATSSSSFLQCSSIIRITDKALREEL
VTLTGGQKHVAQAAEFWVFCADFNRHLQICPDAQLGLAEQLLLGVVDTAMMAQNALIAAE
SLGLGGVYIGGLRNNIEAVTKLLKLPQHVLPLFGLCLGWPADNPDLKPRLPASILVHENS
YQPLDKGALAQYDEQLAEYYLTRGSNNRRDTWSDHIRRTIIKESRPFILDYLHKQGWATR
Structure
1F5V
Pathway Microbial metabolism in diverse environments (ecj01120 )
Nitrotoluene degradation (ecj00633 )
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.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          1 Drugs
Loperamide hydrochloride
 Drug Info Approved Irritable bowel syndrome ICD11: DD91 [1]
      Drugs in Phase 3 Clinical Trial Click to Show/Hide the Full List of Drugs:          2 Drugs
Nitrazepam
 Drug Info Phase 3 Insomnia ICD11: 7A00 [2]
Nitrofural
 Drug Info Phase 3 Acute tonsillitis ICD11: CA03 [2]
      Drugs in Phase 1 Clinical Trial Click to Show/Hide the Full List of Drugs:          1 Drugs
HSDB-674
 Drug Info Phase 1 Rheumatoid arthritis ICD11: FA20 [3]
      Discontinued/withdrawn Drugs Click to Show/Hide the Full List of Drugs:          2 Drugs
CBL-954
 Drug Info Discontinued Hepatocellular carcinoma ICD11: 2C12 [4]
CBL-954
 Drug Info Discontinued Hepatocellular carcinoma ICD11: 2C12 [5]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR005296 CL-205086 Unclear Reduction - Reduction CL-205086 [6]
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.
5 uvrB gene deletion enhances SOS chromotest sensitivity for nitroreductases that preferentially generate the 4-hydroxylamine metabolite of the anti-cancer prodrug CB1954
6 Delamanid is not metabolized by Salmonella or human nitroreductases: a possible mechanism for the lack of mutagenicity. Regul Toxicol Pharmacol. 2017 Mar;84:1-8.

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