Molecule Information

General Information of the Molecule (ID: Mol02125)

• Name: Oxygen-insensitive NAD(P)H nitroreductase (NFSB) ,Escherichia coli
• Synonyms: Oxygen-insensitive NAD(P)H nitroreductase (EC 1.-.-.-) (Dihydropteridine reductase) (EC 1.5.1.34) (FMN-dependent nitroreductase); nfsB; dprA; nfnB; nfsI; ntr; b0578; JW0567
• Molecule Type: Protein
• Gene Name: nfsB
• Gene ID: 945778
• Sequence:
  MDIISVALKRHSTKAFDASKKLTPEQAEQIKTLLQYSPSSTNSQPWHFIVASTEEGKARV
  AKSAAGNYVFNERKMLDASHVVVFCAKTAMDDVWLKLVVDQEDADGRFATPEAKAANDKG
  RKFFADMHRKDLHDDAEWMAKQVYLNVGNFLLGVAALGLDAVPIEGFDAAILDAEFGLKE
  KGYTSLVVVPVGHHSVEDFNATLPKSRLPQNITLTEV
• 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.
• Uniprot ID: NFSB_ECOLI

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: 91347
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Nitrofurazone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Nitrofurazone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: THP1 cells; Pleural effusion; Homo sapiens (Human); CVCL_0006
• Mechanism Description: Escherichia coli contains at least two enzymes which reduce nitrofurazone and other nitrofuran derivatives. One of these enzymes is lacking in some nitrofurazone-resistant mutant strains. We now report that there are three separable nitrofuran reductases in this organism: reductase I (mol. wt. approximately 50 000, insensitive to O2), reductase IIa (mol. wt. approximately 120 000, inhibited by oxygen), reductase IIb (mol. wt. approximately 700 000, inhibited by O2). Unstable metabolites formed during the reduction of nitrofurazone by preparations containing reductases IIa and IIb produce breaks in DNA in vitro. In vivo experiments with nitrofurazone-resistant strains, which lack reductase II but contain reductases IIa and IIb, demonstrated that lethality, mutation, and DNA breakage are all greatly increased when cultures are incubated under anaerobic conditions, i.e., conditions such that reductase II is active. These results provide further evidence for the importance of reductive activation of nitrofurazone.

References

• Ref 1: Nitrofurazone-reducing enzymes in E. coli and their role in drug activation in vivo .Can J Microbiol. 1975 Oct;21(10):1484-91. doi: 10.1139/m75-220. 10.1139/m75-220