The aerobic degradation of 1-(5-nitrofurfurylideneamino)-2-imidazolidinone (NF-246) by Escherichia coli

Gavin, John J.; Ebetino, Frank F.; Freedman, R.; Waterbury, W. E.

doi:10.1016/0003-9861(66)90205-0

Cited by 30 publications

(14 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analysis of purified NfsA confirmed that NfsA uses NADPH but not NADH for nitrofurazone reduction (Table 1). Nitrofurazone appears eventually to be reduced to open-chain nitrile (8), suggesting that, as a whole, six electrons are transferred upon nitrofurazone reduction (22). We are not sure whether NfsA is responsible for all these steps.…”

Section: Resultsmentioning

confidence: 99%

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase

et al. 1996

View full text Add to dashboard Cite

We identified the nfsA gene, encoding the major oxygen-insensitive nitroreductase in Escherichia coli, and determined its position on the E. coli map to be 19 min. We also purified its gene product, NfsA, to homogeneity. It was suggested that NfsA is a nonglobular protein with a molecular weight of 26,799 and is associated tightly with a flavin mononucleotide. Its amino acid sequence is highly similar to that of Frp, a flavin oxidoreductase from Vibrio harveyi (B. Lei, M. Liu, S. Huang, and S.-C. Tu, J. Bacteriol. 176:3552-3558, 1994), an observation supporting the notion that E. coli nitroreductase and luminescent-bacterium flavin reductase families are intimately related in evolution. Although no appreciable sequence similarity was detected between two E. coli nitroreductases, NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a broad electron acceptor specificity similar to those of NfsB. NfsA reduced nitrofurazone by a ping-pong Bi-Bi mechanism possibly to generate a two-electron transfer product.The oxygen-insensitive nitroreductase activity in Escherichia coli consists of one major and two minor components (5). The major component is an NADPH-linked enzyme encoded by nfsA, while minor components, encoded by nfsB and an unidentified gene (5, 19), can use both NADH and NADPH as electron donors. We have cloned and mapped nfsB and analyzed biochemical properties of the purified gene product (NfsB) (29). Our analysis suggested that NfsB is similar in sequence and many biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri (31). NfsB was also found to have a low level of flavin reductase activity (29). Furthermore, a single amino acid substitution of Phe-124 of NfsB changed NfsB into an FRase I-like flavin reductase whose activity was three times higher than that of the authentic FRase I (28). Thus, it is reasonable to assume that genes coding for V. fischeri FRase I and E. coli NfsB nitroreductase are derivatives of a common progenitor gene. Since luminescent bacteria contain several species of flavin reductase (9, 30, 31) and nitroreductase in E. coli forms a family consisting of functionally redundant members (5), as with the NfsB-FRase I pair (29, 31), other nitroreductase members in E. coli might have their counterparts in the flavin reductase family of luminescent bacteria.To clarify the evolutionary and biochemical relationships between flavin reductases of luminescent bacteria and E. coli nitroreductases, gene cloning and biochemical characterization of E. coli nitroreductases other than NfsB may be necessary. Here, we identified the nfsA gene, encoding the major nitroreductase in E. coli, and characterized its gene product, NfsA.Our results showed NfsA nitroreductase to be a flavoprotein associated tightly with flavin mononucleotide (FMN) and to be the ortholog in E. coli of Frp, a flavin oxidoreductase from Vibrio harveyi (11,12,18), an observation supporting a close evolutionary relation between E. coli nitroreductase and luminescent-bacterium flav...

show abstract

Section: Resultsmentioning

confidence: 99%

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase

et al. 1996

View full text Add to dashboard Cite

show abstract

“…The selectivity index (calculated as a ratio of the IC 50 against the mammalian line to the IC 50 against the parasite) for each agent was then determined. In all cases, the 6 (31,43). To identify which products are generated following TbNTR reduction, the 6 most potent nitrofurans were enzymatically reduced and the resultant material analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This results in the formation of an unsaturated open-chain nitrile, which, unlike the parental prodrug, displays equal cytotoxicity toward trypanosomal and mammalian cells. For some nitrofurans, the unsaturated open-chain nitrile can convert rapidly to a nontoxic saturated state (31). Although nifurtimox does undergo this change in vitro, this process occurs at a low rate (25).…”

mentioning

confidence: 99%

Evaluating 5-Nitrofurans as Trypanocidal Agents

Bot

Hall

Álvarez

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…Füran halkasının dahi değiştirilebileeeği akla gelmiş ve Nitrotiyazoııer elde edilmiştir (I, 2) ki bugün Şistozomiyazis'te harika ilaç olarak kullanılan Nirİdazol (I), yada imidazol girmesiyle Nitroimidazoller yapılabilmiş ve bu kökten elde edilen Dimetridazol, Flajil ve Metronidazol çok kısa bir sürede meşhur ilaçlar olmuşlardır (I 2, 13, 35, 39). Son zamanlarda 5-Nitrofüran çekirdeğİne yan dallar olarak sokulmağa çalışılan tiyazol türevIeri (52), amid veya hidrazi t yüklü dİazol ve triazin, yada bunların asetat şekilleri, gliyoksal ile ikinci bir füran halkası (6,17,27,57,65), füranın benzenle yer değiş-tirmesi (62) gibi kimyasal manipülasyonlarla çok sayıda antibiyotik madde sentezlenebilmiştir.…”

Section: Introductionunclassified

“…En basit bir türev olan 5-Nitro-2-füroik asit ile bunun ürünleri olan Fürasin, Nirodoksizon, Nifüraldezon ve kısmen de olsa Füraltadon ve Fürazolidon gibi ilaçlar, çeşitli dokular veya Ksantin oksidaz enzimiyle inkübe edildikte, bunların da ilkin Hidroksilamino ve Aminofüran analoglarına indirgendikleri, son basamakta ise füran halkasının Oksijenle 5 numaralı karbon arasındaki bağın kırılması şeklinde açıldığı, amin kısmının atılmasında Alfa-ketoglutaramik asit yapısında ve bunun da karboksil kısmını kaybetmesi ile meydana gelen karbon iskeletinin çeşitli karbohidrat sentezleri için yapı taşı olabildiği, deaminasyonun Şif bazı teşkili ile meydana geldiği anlaşılmıştır. (27,32,40). Glutatiyon redüktaz (ll) enziminin inhibe edilmesi, bazı kimselerde Glükoz-6-fosfataz enziminin normalolmayabildiği hallerde, glütatiyonun birdenbire düşmesine ve kanda hemolize yol açmaktadır.…”

Section: Introductionunclassified

NİTROFÜRAN TÜREVİ İLAÇLARıN KİMYASAL, FARMAKOLOJİK VE BİYOLOJİK ÖZELLİKLERİ ÜZERİNE DÜŞÜNCELER

Ertürk¹

1971

Ankara Üniversitesi Veteriner Fakültesi Dergisi

View full text Add to dashboard Cite

The aerobic degradation of 1-(5-nitrofurfurylideneamino)-2-imidazolidinone (NF-246) by Escherichia coli

Cited by 30 publications

References 8 publications

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase

Evaluating 5-Nitrofurans as Trypanocidal Agents

NİTROFÜRAN TÜREVİ İLAÇLARıN KİMYASAL, FARMAKOLOJİK VE BİYOLOJİK ÖZELLİKLERİ ÜZERİNE DÜŞÜNCELER

Contact Info

Product

Resources

About