BRENDA - Enzyme Database
show all sequences of 3.6.1.22

Comparative analysis of mycobacterial NADH pyrophosphatase isoforms reveals a novel mechanism for isoniazid and ethionamide inactivation

Wang, X.D.; Gu, J.; Wang, T.; Bi, L.J.; Zhang, Z.P.; Cui, Z.Q.; Wei, H.P.; Deng, J.Y.; Zhang, X.E.; Mol. Microbiol. 82, 1375-1391 (2011)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
expressed in Escherichia coli BL21 (DE3) cells
Mycobacterium tuberculosis
expressed in Escherichia coli BL21 (DE3) cells and in Mycobacterium smegmatis strain mc2155
Mycobacterium tuberculosis variant bovis
Engineering
Amino acid exchange
Commentary
Organism
P237Q
the mutation prevents dimer formation, and results in a loss of enzymatic activity
Mycobacterium tuberculosis
P237Q
the mutation prevents dimer formation, and results in a loss of enzymatic activity
Mycobacterium tuberculosis variant bovis
Inhibitors
Inhibitors
Commentary
Organism
Structure
Ca2+
no activity in the presence of Ca2+
Mycobacterium tuberculosis
Ca2+
no activity in the presence of Ca2+
Mycobacterium tuberculosis variant bovis
Cu2+
no activity in the presence of Cu2+
Mycobacterium tuberculosis
Cu2+
no activity in the presence of Cu2+
Mycobacterium tuberculosis variant bovis
Fe2+
no activity in the presence of Fe2+
Mycobacterium tuberculosis
Fe3+
no activity in the presence of Fe3+
Mycobacterium tuberculosis
Fe3+
no activity in the presence of Fe3+
Mycobacterium tuberculosis variant bovis
Mg2+
no activity in the presence of Mg2+
Mycobacterium tuberculosis
Zn2+
no activity in the presence of Zn2+
Mycobacterium tuberculosis
Zn2+
no activity in the presence of Zn2+
Mycobacterium tuberculosis variant bovis
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Fe2+
the enzyme shows some activity on NADH in the presence of Fe2+
Mycobacterium tuberculosis variant bovis
Mg2+
Mg2+ has highest stimulating effect
Mycobacterium tuberculosis variant bovis
Mn2+
Mn2+ has highest stimulating effect
Mycobacterium tuberculosis
Molecular Weight [Da]
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
40000
-
2 * 40000, SDS-PAGE
Mycobacterium tuberculosis variant bovis
50000
-
gel filtration
Mycobacterium tuberculosis
51000
-
1 * 51000, purified recombinant NudC (fused with Trx tag), calculated from amino acid sequence
Mycobacterium tuberculosis
80000
-
gel filtration
Mycobacterium tuberculosis variant bovis
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Mycobacterium tuberculosis
P9WIX5
-
-
Mycobacterium tuberculosis H37Rv
P9WIX5
-
-
Mycobacterium tuberculosis variant bovis
C1AGW8
-
-
Purification (Commentary)
Commentary
Organism
nickel affinity column chromatography and Superdex 200 gel filtration
Mycobacterium tuberculosis
nickel affinity column chromatography and Superdex 200 gel filtration
Mycobacterium tuberculosis variant bovis
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ethionamide-NAD+ + H2O
-
720498
Mycobacterium tuberculosis variant bovis
ethionamide-NMNH + AMP
-
-
-
?
isoniazid-NAD+ + H2O
-
720498
Mycobacterium tuberculosis variant bovis
isoniazid-NMNH + AMP
-
-
-
?
NAD+ + H2O
weak substrate
720498
Mycobacterium tuberculosis variant bovis
NMN + AMP
-
-
-
?
NAD+ + H2O
weak substrate
720498
Mycobacterium tuberculosis
NMN + AMP
-
-
-
?
NAD+ + H2O
weak substrate
720498
Mycobacterium tuberculosis H37Rv
NMN + AMP
-
-
-
?
NADH + H2O
highest activity with NADH
720498
Mycobacterium tuberculosis variant bovis
NMNH + AMP
-
-
-
?
NADH + H2O
highest activity with NADH
720498
Mycobacterium tuberculosis
NMNH + AMP
-
-
-
?
NADH + H2O
highest activity with NADH
720498
Mycobacterium tuberculosis H37Rv
NMNH + AMP
-
-
-
?
Subunits
Subunits
Commentary
Organism
homodimer
2 * 40000, SDS-PAGE
Mycobacterium tuberculosis variant bovis
monomer
1 * 50000, SDS-PAGE; 1 * 51000, purified recombinant NudC (fused with Trx tag), calculated from amino acid sequence
Mycobacterium tuberculosis
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
40
-
-
Mycobacterium tuberculosis variant bovis
Temperature Range [°C]
Temperature Minimum [°C]
Temperature Maximum [°C]
Commentary
Organism
35
45
enzyme activity rapidly decreases below 35°C or above 45°C
Mycobacterium tuberculosis variant bovis
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
enzyme activity rapidly decreases below pH 7.5
Mycobacterium tuberculosis variant bovis
Cloned(Commentary) (protein specific)
Commentary
Organism
expressed in Escherichia coli BL21 (DE3) cells
Mycobacterium tuberculosis
expressed in Escherichia coli BL21 (DE3) cells and in Mycobacterium smegmatis strain mc2155
Mycobacterium tuberculosis variant bovis
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
P237Q
the mutation prevents dimer formation, and results in a loss of enzymatic activity
Mycobacterium tuberculosis
P237Q
the mutation prevents dimer formation, and results in a loss of enzymatic activity
Mycobacterium tuberculosis variant bovis
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
Ca2+
no activity in the presence of Ca2+
Mycobacterium tuberculosis
Ca2+
no activity in the presence of Ca2+
Mycobacterium tuberculosis variant bovis
Cu2+
no activity in the presence of Cu2+
Mycobacterium tuberculosis
Cu2+
no activity in the presence of Cu2+
Mycobacterium tuberculosis variant bovis
Fe2+
no activity in the presence of Fe2+
Mycobacterium tuberculosis
Fe3+
no activity in the presence of Fe3+
Mycobacterium tuberculosis
Fe3+
no activity in the presence of Fe3+
Mycobacterium tuberculosis variant bovis
Mg2+
no activity in the presence of Mg2+
Mycobacterium tuberculosis
Zn2+
no activity in the presence of Zn2+
Mycobacterium tuberculosis
Zn2+
no activity in the presence of Zn2+
Mycobacterium tuberculosis variant bovis
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Fe2+
the enzyme shows some activity on NADH in the presence of Fe2+
Mycobacterium tuberculosis variant bovis
Mg2+
Mg2+ has highest stimulating effect
Mycobacterium tuberculosis variant bovis
Mn2+
Mn2+ has highest stimulating effect
Mycobacterium tuberculosis
Molecular Weight [Da] (protein specific)
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
40000
-
2 * 40000, SDS-PAGE
Mycobacterium tuberculosis variant bovis
50000
-
gel filtration
Mycobacterium tuberculosis
51000
-
1 * 51000, purified recombinant NudC (fused with Trx tag), calculated from amino acid sequence
Mycobacterium tuberculosis
80000
-
gel filtration
Mycobacterium tuberculosis variant bovis
Purification (Commentary) (protein specific)
Commentary
Organism
nickel affinity column chromatography and Superdex 200 gel filtration
Mycobacterium tuberculosis
nickel affinity column chromatography and Superdex 200 gel filtration
Mycobacterium tuberculosis variant bovis
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ethionamide-NAD+ + H2O
-
720498
Mycobacterium tuberculosis variant bovis
ethionamide-NMNH + AMP
-
-
-
?
isoniazid-NAD+ + H2O
-
720498
Mycobacterium tuberculosis variant bovis
isoniazid-NMNH + AMP
-
-
-
?
NAD+ + H2O
weak substrate
720498
Mycobacterium tuberculosis variant bovis
NMN + AMP
-
-
-
?
NAD+ + H2O
weak substrate
720498
Mycobacterium tuberculosis
NMN + AMP
-
-
-
?
NAD+ + H2O
weak substrate
720498
Mycobacterium tuberculosis H37Rv
NMN + AMP
-
-
-
?
NADH + H2O
highest activity with NADH
720498
Mycobacterium tuberculosis variant bovis
NMNH + AMP
-
-
-
?
NADH + H2O
highest activity with NADH
720498
Mycobacterium tuberculosis
NMNH + AMP
-
-
-
?
NADH + H2O
highest activity with NADH
720498
Mycobacterium tuberculosis H37Rv
NMNH + AMP
-
-
-
?
Subunits (protein specific)
Subunits
Commentary
Organism
homodimer
2 * 40000, SDS-PAGE
Mycobacterium tuberculosis variant bovis
monomer
1 * 50000, SDS-PAGE; 1 * 51000, purified recombinant NudC (fused with Trx tag), calculated from amino acid sequence
Mycobacterium tuberculosis
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
40
-
-
Mycobacterium tuberculosis variant bovis
Temperature Range [°C] (protein specific)
Temperature Minimum [°C]
Temperature Maximum [°C]
Commentary
Organism
35
45
enzyme activity rapidly decreases below 35°C or above 45°C
Mycobacterium tuberculosis variant bovis
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
enzyme activity rapidly decreases below pH 7.5
Mycobacterium tuberculosis variant bovis
General Information
General Information
Commentary
Organism
malfunction
deletion of the NADH pyrophosphatase gene nudC results in increased susceptibility to isoniazid and ethionamide
Mycobacterium tuberculosis variant bovis
physiological function
NADH pyrophosphatase NudC plays an important role in the inactivation of isoniazid and ethionamide
Mycobacterium tuberculosis variant bovis
General Information (protein specific)
General Information
Commentary
Organism
malfunction
deletion of the NADH pyrophosphatase gene nudC results in increased susceptibility to isoniazid and ethionamide
Mycobacterium tuberculosis variant bovis
physiological function
NADH pyrophosphatase NudC plays an important role in the inactivation of isoniazid and ethionamide
Mycobacterium tuberculosis variant bovis
Other publictions for EC 3.6.1.22
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
733748
Wang
Identification of UshA as a ma ...
Escherichia coli, Escherichia coli DH10B
Enzyme Microb. Technol.
58-59
75-79
2014
-
-
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3
-
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2
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3
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-
4
-
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-
3
-
-
-
-
-
1
1
-
3
3
720498
Wang
Comparative analysis of mycoba ...
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv, Mycobacterium tuberculosis variant bovis
Mol. Microbiol.
82
1375-1391
2011
-
-
2
-
2
-
10
-
-
3
4
-
-
8
-
-
2
-
-
-
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8
2
1
1
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-
1
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2
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2
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10
-
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3
4
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2
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8
2
1
1
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1
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2
2
-
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-
670632
Jambunathan
Analysis of Arabidopsis growth ...
Arabidopsis sp.
Planta
224
1-11
2006
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-
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1
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668217
Magni
Enzymology of NAD+ homeostasis ...
Homo sapiens
Cell. Mol. Life Sci.
61
19-34
2004
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1
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1
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1
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1
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654332
AbdelRaheim
The NADH diphosphatase encoded ...
Saccharomyces cerevisiae
Arch. Biochem. Biophys.
388
18-24
2001
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-
1
-
-
-
-
3
1
-
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1
-
1
-
1
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7
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1
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3
1
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1
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1
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7
-
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-
-
-
-
-
-
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-
-
-
-
-
-
655747
Schmidt-Brauns
Is a NAD pyrophosphatase activ ...
Haemophilus influenzae
Int. J. Med. Microbiol.
291
219-225
2001
-
-
-
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1
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4
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2
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1
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1
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2
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1
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-
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656433
Bortell
Nicotinamide adenine dinucleot ...
Rattus norvegicus
J. Immunol.
167
2049-2059
2001
-
1
-
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1
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1
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1
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1
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1
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1
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209959
Xu
Cloning and characterization o ...
Caenorhabditis elegans, Escherichia coli, Saccharomyces cerevisiae
Biochem. Biophys. Res. Commun.
273
753-758
2000
-
-
2
-
-
-
4
4
-
6
4
3
-
6
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2
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19
3
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4
3
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2
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4
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4
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6
4
3
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2
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19
3
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4
3
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209958
Hagen
Detection and identification o ...
Rattus norvegicus
Biochim. Biophys. Acta
1340
7-12
1997
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1
1
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2
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1
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209957
Frick
Cloning, purification, and pro ...
Escherichia coli
J. Biol. Chem.
270
1529-1534
1995
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1
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1
6
-
5
2
1
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2
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1
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13
1
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1
1
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1
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1
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1
1
6
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5
2
1
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1
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13
1
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1
1
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171771
Wagner
The pyridine-nucleotide cycle ...
Nicotiana tabacum
Planta
167
226-232
1986
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1
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1
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4
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171772
Wagner
Regulation in tobacco callus o ...
Nicotiana tabacum
Planta
168
408-413
1986
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209954
Falconer
-
Membrane association of NAD py ...
Salmonella enterica subsp. enterica serovar Typhimurium
Curr. Microbiol.
10
237-242
1984
-
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1
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1
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1
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1
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171773
Foster
Pyridine nucleotide cycle of S ...
Salmonella enterica subsp. enterica serovar Typhimurium
J. Bacteriol.
145
1002-1009
1981
-
-
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2
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209952
Berghaeuser
-
A simple preparation of an enz ...
Solanum tuberosum
Biotechnol. Lett.
3
339-344
1981
-
1
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-
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1
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1
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209951
Davies
An enzyme degrading reduced ni ...
Proteus vulgaris
Biochem. J.
175
669-674
1978
1
-
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5
-
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4
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2
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1
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2
1
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2
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1
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5
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4
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1
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2
1
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2
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209950
Jeck
Simple methods of preparing ni ...
Solanum tuberosum
FEBS Lett.
42
161-164
1974
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209949
Nakajima
Purification and properties of ...
Proteus vulgaris
Biochim. Biophys. Acta
293
242-255
1973
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209948
Anderson
Nicotinamide-adenin dinucleoti ...
Aedes aegypti
Biochem. J.
101
392-396
1966
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