Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DME1048)
DME Name Oxygen-insensitive NADPH nitroreductase B (nfsB), Escherichia coli
Synonyms Oxygen-insensitive NAD(P)H nitroreductase B; Dihydropteridine reductase; FMN-dependent nitroreductase; JW0567; b0578; ntr; pnrB
Gene Name nfsB
UniProt ID
NFSB_ECOLI
Gene ID
945778
EC Number    EC: 1.5.1.34     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.34
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
MDIISVALKRHSTKAFDASKKLTPEQAEQIKTLLQYSPSSTNSQPWHFIVASTEEGKARV
AKSAAGNYVFNERKMLDASHVVVFCAKTAMDDVWLKLVVDQEDADGRFATPEAKAANDKG
RKFFADMHRKDLHDDAEWMAKQVYLNVGNFLLGVAALGLDAVPIEGFDAAILDAEFGLKE
KGYTSLVVVPVGHHSVEDFNATLPKSRLPQNITLTEV
Structure
1DS7 ; 1ICR ; 1ICU ; 1ICV ; 1IDT ; 1OO5 ; 1OO6 ; 1OON ; 1OOQ ; 1YKI ; 1YLR ; 1YLU ; 3X21 ; 3X22
Pathway Microbial metabolism in diverse environments (ecj01120 )
Nitrotoluene degradation (ecj00633 )
Function This enzyme can reduce a variety of nitroaromatic compounds using NADH (and to lesser extent NADPH) as source of reducing equivalents; two electrons are transferred. And it can reduce nitrofurazone, quinones and the anti-tumor agent CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide).
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          2 Drugs
Nifurtimox
 Drug Info Approved Chagas disease ICD11: 1F53 [1]
Clonazepam
 Drug Info Approved Epilepsy ICD11: 8A60 [2]
      Drugs in Phase 4 Clinical Trial Click to Show/Hide the Full List of Drugs:          1 Drugs
Flunitrazepam
 Drug Info Phase 4 Insomnia ICD11: 7A00 [3]
      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 [4]
Nitrofural
 Drug Info Phase 3 Acute tonsillitis ICD11: CA03 [4]
      Discontinued/withdrawn Drugs Click to Show/Hide the Full List of Drugs:          1 Drugs
CBL-954
 Drug Info Discontinued Hepatocellular carcinoma ICD11: 2C12 [4], [5]
      Preclinical/investigative Agents Click to Show/Hide the Full List of Drugs:          3 Drugs
Misonidazole
 Drug Info Investigative Discovery agent ICD: N.A. [6]
Nitrobenzodiazepine
 Drug Info Investigative Discovery agent ICD: N.A. [3]
Nitrobenzodiazepine
 Drug Info Investigative Discovery agent ICD: N.A. [2], [3]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR005923 CBL-954 The hydroxylamine metabolite Unclear - Unclear CBL-954 [7]
MR005296 CL-205086 Unclear Reduction - Reduction CL-205086 [8]
MR007195 Flunitrazepam 7-amino-unitrazepam Reduction - Reduction Flunitrazepam [3], [9], [10]
MR005550 Nifurtimox Nifurtimox M2 Reduction - Reduction Nifurtimox [1]
MR005551 Nifurtimox Nifurtimox M1 Reduction - Reduction Nifurtimox [1]
MR005552 Nifurtimox Nifurtimox M17 Reduction - Reduction Nifurtimox [1], [11]
MR004374 Nitrobenzodiazepine 7-Amino-benzodiazepine Reduction - Reduction Nitrobenzodiazepine [2], [3]
⏷ Show the Full List of 7 MR(s)
References
1 Structural and Mechanistic Investigation of the Unusual Metabolism of Nifurtimox
2 Characterization of Escherichia coli nitroreductase NfsB in the metabolism of nitrobenzodiazepines. Biochem Pharmacol. 2009 Jul 1;78(1):96-103.
3 Structure-based development of bacterial nitroreductase against nitrobenzodiazepine-induced hypnosis. Biochem Pharmacol. 2012 Jun 15;83(12):1690-9.
4 Conversion of NfsB, a minor Escherichia coli nitroreductase, to a flavin reductase similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri, by a single amino acid substitution. J Bacteriol. 1996 Aug;178(15):4731-3.
5 Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954. Biochem Pharmacol. 2010 Mar 1;79(5):678-87.
6 Metronidazole (flagyl) and misonidazole (Ro-07-0582): reduction by facultative anaerobes and cytotoxic action on hypoxic bacteria and mammalian cells in vivo. Br J Cancer Suppl. 1978 Jun;3:132-5.
7 Bystander or no bystander for gene directed enzyme prodrug therapy
8 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.
9 NADPH-cytochrome P-450 reductase is involved in flunitrazepam reductive metabolism in Hep G2 and Hep 3B cells
10 Flunitrazepam oxidative metabolism in human liver microsomes: involvement of CYP2C19 and CYP3A4. Xenobiotica. 1999 Oct;29(10):973-86.
11 Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites

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