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Literature summary extracted from

  • Green, L.K.; Syddall, S.P.; Carlin, K.M.; Bell, G.D.; Guise, C.P.; Mowday, A.M.; Hay, M.P.; Smaill, J.B.; Patterson, A.V.; Ackerley, D.F.
    Pseudomonas aeruginosa NfsB and nitro-CBI-DEI - a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy (2013), Mol. Cancer, 12, 58 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.7.1.B2 pharmacology Pseudomonas aeruginosa NfsB and nitro-CBI-DEI is a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy Pseudomonas aeruginosa

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.7.1.B2 gene nfsB, recombinant overexpression in Escherichia coli reporter strain SOS-R2, which contains a lacZ reporter gene under control of the SOS responsive promoter sfiA, functional nitroreductase NfsB expression in human HCT-116 cells Pseudomonas aeruginosa
1.7.1.B2 gene nfsB, recombinant overexpression in Escherichia coli reporter strain SOS-R2, which contains a lacZ reporter gene under control of the SOS responsive promoter sfiA, functional nitroreductase NfsB expression in human HCT-116 cells Escherichia coli
1.7.1.B3 gene nfsA, recombinant overexpression in Escherichia coli reporter strain SOS-R2, which contains a lacZ reporter gene under control of the SOS responsive promoter sfiA, functional nitroreductase NfsA expression in human HCT-116 cells Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.7.1.B2 additional information Escherichia coli Escherichia coli nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA ?
-
?
1.7.1.B2 additional information Pseudomonas aeruginosa Pseudomonas aeruginosa nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA ?
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.7.1.B2 Escherichia coli P38489
-
-
1.7.1.B2 Pseudomonas aeruginosa Q9HTZ9
-
-
1.7.1.B3 Escherichia coli P17117
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.7.1.B2 5-(aziridin-1-yl)-2,4-dinitrobenzamide + NAD(P)H + H+ i.e. CB1954, an aziridinyl dinitrobenzamide prodrug Escherichia coli ? + NAD(P)+
-
?
1.7.1.B2 5-(aziridin-1-yl)-2,4-dinitrobenzamide + NAD(P)H + H+ i.e. CB1954, an aziridinyl dinitrobenzamide prodrug, low activity Pseudomonas aeruginosa ? + NAD(P)+
-
?
1.7.1.B2 additional information Escherichia coli nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA Escherichia coli ?
-
?
1.7.1.B2 additional information Pseudomonas aeruginosa nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA Pseudomonas aeruginosa ?
-
?
1.7.1.B2 additional information an intrinsically oxygen-insensitive nature of the two-electron reduction mechanism Pseudomonas aeruginosa ?
-
?
1.7.1.B2 additional information an intrinsically oxygen-insensitive nature of the two-electron reduction mechanism Escherichia coli ?
-
?
1.7.1.B2 nitro-CBI-5-[(dimethylamino)ethoxy]indole + NAD(P)H + H+ a nitro-CBI prodrug, high activity Pseudomonas aeruginosa ? + NAD(P)+
-
?
1.7.1.B2 nitro-CBI-5-[(dimethylamino)ethoxy]indole + NAD(P)H + H+ a nitro-CBI prodrug, low activity Escherichia coli ? + NAD(P)+
-
?
1.7.1.B3 5-(aziridin-1-yl)-2,4-dinitrobenzamide + NADPH + H+ i.e. CB1954, an aziridinyl dinitrobenzamide prodrug Escherichia coli ? + NADP+
-
?
1.7.1.B3 additional information an intrinsically oxygen-insensitive nature of the two-electron reduction mechanism Escherichia coli ?
-
?
1.7.1.B3 nitro-CBI-5-[(dimethylamino)ethoxy]indole + NAD(P)H + H+ a nitro-CBI prodrug, low activity Escherichia coli ? + NAD(P)+
-
?

Synonyms

EC Number Synonyms Comment Organism
1.7.1.B2 NfsB
-
Pseudomonas aeruginosa
1.7.1.B2 NfsB
-
Escherichia coli
1.7.1.B2 NfsB_Ec
-
Escherichia coli
1.7.1.B2 NfsB_Pa
-
Pseudomonas aeruginosa
1.7.1.B3 NfsA
-
Escherichia coli
1.7.1.B3 nitroreductase A
-
Escherichia coli

General Information

EC Number General Information Comment Organism
1.7.1.B2 physiological function Escherichia coli NfsB expressing HCT-116 cells are 23.5fold more sensitive to prodrug nitro-CBI-DEI than pure cultures of untransfected cells, monolayer cytotoxicity assays using human colon carcinoma HCT-116 cells. The discrepancy in the fold-sensitivity to nitro-CBI-DEI between the two and three dimensional cytotoxicity assays stems from loss of activated drug into the media in the monolayer cultures Escherichia coli
1.7.1.B2 physiological function Pseudomonas aeruginosa NfsB expressing HCT-116 cells are 540fold more sensitive to prodrug nitro-CBI-DEI than pure cultures of untransfected cells, the activated drug that they generate also displays an unprecedented local bystander effect, monolayer cytotoxicity assays using human colon carcinoma HCT-116 cells. The discrepancy in the fold-sensitivity to nitro-CBI-DEI between the two and three dimensional cytotoxicity assays stems from loss of activated drug into the media in the monolayer cultures Pseudomonas aeruginosa