Literature summary for 1.7.1.B3 extracted from

Valiauga, B.; Williams, E.M.; Ackerley, D.F.; Cenas, N.
Reduction of quinones and nitroaromatic compounds by Escherichia coli nitroreductase A (NfsA) Characterization of kinetics and substrate specificity (2017), Arch. Biochem. Biophys., 614, 14-22 .

Search for more literature for 1.7.1.B3

Application

Application	Comment	Organism
environmental protection	NfsA has potential applications in the biodegradation of nitroaromatic environment pollutants, e.g. explosives	Escherichia coli
medicine	NfsA has potential applications in the anticancer strategy gene-directed enzyme prodrug therapy	Escherichia coli

Inhibitors

Inhibitors	Comment	Organism	Structure
dicoumarol	inhibits Escherichia coli enzyme NfsB far more strongly than enzyme NfsA, by acting as a competitive inhibitor towards NADPH, uncompetitive towards substrate tetryl	Escherichia coli
NADP+	inhibition of NfsA-catalyzed tetryl reduction by NADP+	Escherichia coli

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	Michaelis-Menten steady-state kinetics. For NfsA the oxidative half-reaction (i.e., the reoxidation of FMNH by the oxidant substrate) is a rate-limiting step, because the values of kcat at infinite concentrations of tetryl or 2,4,6-trinitrotoluene are substantially lower than the lowest rate of the reductive half reaction (the reduction of FMN by NADPH) measured in the preliminary rapid reaction experiments. Stopped-flow and single-turnover measurements	Escherichia coli
0.011	-	tetryl	pH 7.0, 25°C	Escherichia coli
0.018	-	o-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
0.019	-	Nitrofurantoin	pH 7.0, 25°C	Escherichia coli
0.031	-	nifuroxime	pH 7.0, 25°C	Escherichia coli
0.033	-	2,4,6-trinitrotoluene	pH 7.0, 25°C	Escherichia coli
0.037	-	p-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
0.046	-	m-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
0.17	-	p-nitrobenzaldehyde	pH 7.0, 25°C	Escherichia coli
0.23	-	5-(aziridin-1-yl)-2,4-dinitrobenzamide	pH 7.0, 25°C	Escherichia coli
0.39	-	p-nitroacetophenone	pH 7.0, 25°C	Escherichia coli
1.5	-	nitrobenzene	pH 7.0, 25°C	Escherichia coli
2.5	-	p-nitrobenzoic acid	pH 7.0, 25°C	Escherichia coli

Organism

Organism	UniProt	Comment	Textmining
Escherichia coli	-	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
an aromatic amine + 3 NADP+ + 2 H2O = an aromatic nitrate + 3 NADPH + 3 H+	catalytic mechanism analysis, two (four)-electron reduction of nitrobenzenes and single-step (H-) hydride transfer mechanism. NfsA follows a ping-pong mechanism, overview	Escherichia coli	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2,4,6-trinitrotoluene + NADPH + H+	-	Escherichia coli	? + NADP+ + H2O	-	?
5-(aziridin-1-yl)-2,4-dinitrobenzamide + NADPH + H+	i.e. CB1954, an aziridinyl dinitrobenzamide prodrug	Escherichia coli	? + NADP+	-	?
m-dinitrobenzene + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
additional information	NADPH-dependent reduction of quinones, cf. EC 1.6.5.5, and nitroaromatic compounds by NfsA, overview. The reactivity of nitroaromatic compounds (log kcat/Km) follows a linear dependence on their single-electron reduction potential, indicating a limited role for compound structure or active site flexibility in their reactivity. The reactivity of quinones is lower than that of nitroaromatics having similar single-electron reduction potential values, except for the significantly enhanced reactivity of 2-OH-1,4-naphthoquinones. The reduction of quinones by NfsA is most consistent with a single-step (H-) hydride transfer mechanism, quantitative analysis of two-electron reduction of quinones and nitroaromatics, overview	Escherichia coli	?	-	?
nifuroxime + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
nitrobenzene + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
nitrofurantoin + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
o-dinitrobenzene + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
p-dinitrobenzene + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
p-nitroacetophenone + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
p-nitrobenzaldehyde + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
p-nitrobenzoic acid + NADPH + H+	-	Escherichia coli	? + NADP+	-	?
tetryl + NADPH + H+	-	Escherichia coli	? + NADP+	-	?

Synonyms

Synonyms	Comment	Organism
More	cf. EC 1.6.5.5	Escherichia coli
NfsA	-	Escherichia coli
nitroreductase A	-	Escherichia coli

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	Escherichia coli

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
14	-	nitrobenzene	pH 7.0, 25°C	Escherichia coli
15	-	5-(aziridin-1-yl)-2,4-dinitrobenzamide	pH 7.0, 25°C	Escherichia coli
27	-	p-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
30	-	p-nitrobenzaldehyde	pH 7.0, 25°C	Escherichia coli
55	-	m-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
59	-	p-nitroacetophenone	pH 7.0, 25°C	Escherichia coli
60	-	o-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
64	-	p-nitrobenzoic acid	pH 7.0, 25°C	Escherichia coli
85	-	tetryl	pH 7.0, 25°C	Escherichia coli
89	-	2,4,6-trinitrotoluene	pH 7.0, 25°C	Escherichia coli
136	-	Nitrofurantoin	pH 7.0, 25°C	Escherichia coli
180	-	nifuroxime	pH 7.0, 25°C	Escherichia coli

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7	-	assay at	Escherichia coli

Cofactor

Cofactor	Comment	Organism	Structure
FMN	prosthetic group involved in the reaction	Escherichia coli
NADPH	-	Escherichia coli

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
additional information	-	additional information	inhibition kinetics	Escherichia coli
0.018	-	dicoumarol	pH 7.0, 25°C	Escherichia coli

General Information

General Information	Comment	Organism
additional information	comparisons of the quantitative structure-activity relationships of single-electron reduction of quinones and nitroaromatic compounds by dehydrogenase (electron transferase) flavoenzymes, overview	Escherichia coli
physiological function	NfsA has potential applications in the biodegradation of nitroaromatic environment pollutants, e.g. explosives, and is also of interest for the anticancer strategy gene-directed enzyme prodrug therapy	Escherichia coli

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism	Structure
9.3	-	nitrobenzene	pH 7.0, 25°C	Escherichia coli
25.6	-	p-nitrobenzoic acid	pH 7.0, 25°C	Escherichia coli
65.2	-	5-(aziridin-1-yl)-2,4-dinitrobenzamide	pH 7.0, 25°C	Escherichia coli
151.3	-	p-nitroacetophenone	pH 7.0, 25°C	Escherichia coli
176.5	-	p-nitrobenzaldehyde	pH 7.0, 25°C	Escherichia coli
729.7	-	p-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
1195.7	-	m-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
2697	-	2,4,6-trinitrotoluene	pH 7.0, 25°C	Escherichia coli
3333.3	-	o-dinitrobenzene	pH 7.0, 25°C	Escherichia coli
5806.5	-	nifuroxime	pH 7.0, 25°C	Escherichia coli
7157.9	-	Nitrofurantoin	pH 7.0, 25°C	Escherichia coli
7727.27	-	tetryl	pH 7.0, 25°C	Escherichia coli

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Release 2023.1 (January 2023)