BRENDA - Enzyme Database show
show all sequences of 3.5.1.19

Kinetics and inhibition of nicotinamidase from Mycobacterium tuberculosis

Seiner, D.R.; Hegde, S.S.; Blanchard, J.S.; Biochemistry 49, 9613-9619 (2010)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
expressed in Escherichia coli BL21(DE3) cells
Mycobacterium tuberculosis
Engineering
Amino acid exchange
Commentary
Organism
H57D
the mutant has reduced Mn2+ content and shows a 6fold and 38fold decrease in kcat value for nicotinamide and pyrazinamide, respectively
Mycobacterium tuberculosis
Inhibitors
Inhibitors
Commentary
Organism
Structure
3-pyridine carboxaldehyde
competitive inhibitor
Mycobacterium tuberculosis
iodoacetamide
reversible, competitive inhibitor
Mycobacterium tuberculosis
pyrazinecarbonitrile
irreversible inactivator
Mycobacterium tuberculosis
pyridine-3-carbonitrile
reversible, competitive inhibitor
Mycobacterium tuberculosis
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.013
-
nicotinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.014
-
nicotinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.016
-
Pyrazinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.3
-
Pyrazinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Fe2+
the enzyme contains 0.47 M of Fe2+ per mol of enzyme
Mycobacterium tuberculosis
Mn2+
the enzyme contains 0.44 M Mn2+ per mol of enzyme
Mycobacterium tuberculosis
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
nicotinamide + H2O
Mycobacterium tuberculosis
-
nicotinate + NH3
-
-
?
nicotinamide + H2O
Mycobacterium tuberculosis H37Rv
-
nicotinate + NH3
-
-
?
pyrazinamide + H2O
Mycobacterium tuberculosis
-
pyrazine-2-carboxylic acid + NH3
-
-
?
pyrazinamide + H2O
Mycobacterium tuberculosis H37Rv
-
pyrazine-2-carboxylic acid + NH3
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Mycobacterium tuberculosis
-
-
-
Mycobacterium tuberculosis H37Rv
-
-
-
Purification (Commentary)
Commentary
Organism
Ni-NTA column chromatography
Mycobacterium tuberculosis
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
nicotinamide + H2O
-
718885
Mycobacterium tuberculosis
nicotinate + NH3
-
-
-
?
nicotinamide + H2O
-
718885
Mycobacterium tuberculosis H37Rv
nicotinate + NH3
-
-
-
?
pyrazinamide + H2O
-
718885
Mycobacterium tuberculosis
pyrazine-2-carboxylic acid + NH3
-
-
-
?
pyrazinamide + H2O
-
718885
Mycobacterium tuberculosis H37Rv
pyrazine-2-carboxylic acid + NH3
-
-
-
?
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.1
-
Pyrazinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.5
-
nicotinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
3.1
-
nicotinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
3.8
-
Pyrazinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
around pH 8.0
Mycobacterium tuberculosis
Ki Value [mM]
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
0.00029
-
3-pyridine carboxaldehyde
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.1
-
pyridine-3-carbonitrile
Ki about 0.1 mM, wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
Cloned(Commentary) (protein specific)
Commentary
Organism
expressed in Escherichia coli BL21(DE3) cells
Mycobacterium tuberculosis
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
H57D
the mutant has reduced Mn2+ content and shows a 6fold and 38fold decrease in kcat value for nicotinamide and pyrazinamide, respectively
Mycobacterium tuberculosis
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
3-pyridine carboxaldehyde
competitive inhibitor
Mycobacterium tuberculosis
iodoacetamide
reversible, competitive inhibitor
Mycobacterium tuberculosis
pyrazinecarbonitrile
irreversible inactivator
Mycobacterium tuberculosis
pyridine-3-carbonitrile
reversible, competitive inhibitor
Mycobacterium tuberculosis
Ki Value [mM] (protein specific)
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
0.00029
-
3-pyridine carboxaldehyde
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.1
-
pyridine-3-carbonitrile
Ki about 0.1 mM, wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.013
-
nicotinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.014
-
nicotinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.016
-
Pyrazinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.3
-
Pyrazinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Fe2+
the enzyme contains 0.47 M of Fe2+ per mol of enzyme
Mycobacterium tuberculosis
Mn2+
the enzyme contains 0.44 M Mn2+ per mol of enzyme
Mycobacterium tuberculosis
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
nicotinamide + H2O
Mycobacterium tuberculosis
-
nicotinate + NH3
-
-
?
nicotinamide + H2O
Mycobacterium tuberculosis H37Rv
-
nicotinate + NH3
-
-
?
pyrazinamide + H2O
Mycobacterium tuberculosis
-
pyrazine-2-carboxylic acid + NH3
-
-
?
pyrazinamide + H2O
Mycobacterium tuberculosis H37Rv
-
pyrazine-2-carboxylic acid + NH3
-
-
?
Purification (Commentary) (protein specific)
Commentary
Organism
Ni-NTA column chromatography
Mycobacterium tuberculosis
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
nicotinamide + H2O
-
718885
Mycobacterium tuberculosis
nicotinate + NH3
-
-
-
?
nicotinamide + H2O
-
718885
Mycobacterium tuberculosis H37Rv
nicotinate + NH3
-
-
-
?
pyrazinamide + H2O
-
718885
Mycobacterium tuberculosis
pyrazine-2-carboxylic acid + NH3
-
-
-
?
pyrazinamide + H2O
-
718885
Mycobacterium tuberculosis H37Rv
pyrazine-2-carboxylic acid + NH3
-
-
-
?
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.1
-
Pyrazinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
0.5
-
nicotinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
3.1
-
nicotinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
3.8
-
Pyrazinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
around pH 8.0
Mycobacterium tuberculosis
General Information
General Information
Commentary
Organism
metabolism
the enzyme is involved in the NAD+ salvage pathway
Mycobacterium tuberculosis
General Information (protein specific)
General Information
Commentary
Organism
metabolism
the enzyme is involved in the NAD+ salvage pathway
Mycobacterium tuberculosis
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
6.2
-
Pyrazinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
13
-
Pyrazinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
37
-
nicotinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
220
-
nicotinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
KCat/KM [mM/s] (protein specific)
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
6.2
-
Pyrazinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
13
-
Pyrazinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
37
-
nicotinamide
mutant enzyme H57D, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
220
-
nicotinamide
wild type enzyme, in 100 mM HEPES at pH 8.0 and 25°C
Mycobacterium tuberculosis
Other publictions for EC 3.5.1.19
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)
727053
Stekhanova
Nicotinamidase from the thermo ...
Acidilobus saccharovorans, Acidilobus saccharovorans DSM 16705
Biochemistry
79
54-61
2014
2
-
1
-
-
-
4
1
-
1
1
-
-
7
-
-
-
-
-
-
-
-
2
1
1
1
2
1
1
-
-
-
-
-
-
2
-
1
-
-
-
-
-
4
-
1
-
1
1
-
-
-
-
-
-
-
-
-
2
1
1
1
2
1
1
-
-
-
-
1
1
-
1
1
729184
Stekhanova
Nicotinamidase from the thermo ...
Acidilobus saccharovorans, Acidilobus saccharovorans DSM 16705
Biochemistry (Moscow)
79
54-61
2014
3
-
1
-
-
-
3
2
-
1
1
-
-
7
-
-
-
-
-
-
-
-
6
1
1
1
2
2
1
1
-
-
-
-
-
3
-
1
-
-
-
-
-
3
-
2
-
1
1
-
-
-
-
-
-
-
-
-
6
1
1
1
2
2
1
1
-
-
-
-
-
-
2
2
734741
Ion
A multi-scale computational st ...
Streptococcus pneumoniae
Molecules
19
15735-15753
2014
-
1
-
-
-
-
-
-
-
1
-
1
-
2
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
3
3
-
-
-
735324
Rueda
Nicotinamidase/pyrazinamidase ...
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Tuberculosis
94
644-648
2014
-
-
1
-
-
-
-
-
-
-
1
4
-
3
-
-
1
-
-
-
-
-
4
2
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
4
-
-
-
1
-
-
-
-
4
2
-
-
-
-
-
-
-
-
-
1
1
-
-
-
735084
Sanchez-Carron
Biochemical and mutational ana ...
Oceanobacillus iheyensis, Oceanobacillus iheyensis HTE831
PLoS ONE
8
e56727
2013
-
-
1
-
9
-
2
27
-
2
2
4
-
5
-
-
1
-
-
-
28
-
12
1
1
1
1
26
1
1
1
-
2
-
-
-
-
1
-
-
9
-
-
2
2
27
-
2
2
4
-
-
-
1
-
-
28
-
12
1
1
1
1
26
1
1
1
-
-
2
2
-
26
26
718924
Smith
Structural and kinetic isotope ...
Saccharomyces cerevisiae
Biochemistry
51
243-256
2012
-
-
1
1
10
-
6
8
-
1
-
1
-
6
-
-
1
-
-
-
-
-
7
-
-
-
-
12
1
-
-
-
5
-
-
-
-
1
-
1
10
-
-
6
5
8
-
1
-
1
-
-
-
1
-
-
-
-
7
-
-
-
-
12
1
-
-
-
-
-
-
-
15
15
719619
Gazanion
Leishmania infantum nicotinami ...
Leishmania infantum
Int. J. Parasitol.
42
323-327
2012
-
-
-
-
1
-
-
-
-
-
-
1
-
5
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
735054
Zhang
Molecular dynamics simulations ...
Acinetobacter baumannii, Streptococcus pneumoniae
PLoS ONE
7
e39546
2012
-
-
-
2
-
-
-
-
-
-
-
4
-
3
-
-
-
-
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
4
-
-
-
-
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
720499
Gazanion
The Leishmania nicotinamidase ...
Leishmania infantum, Leishmania infantum MHOM/MA/67/ITMAP-263
Mol. Microbiol.
82
21-38
2011
-
-
1
1
1
-
-
-
1
-
2
4
-
7
-
-
1
-
-
1
-
-
4
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
1
-
-
-
-
-
1
-
2
4
-
-
-
1
-
1
-
-
4
1
-
-
-
-
-
-
-
-
-
2
2
-
-
-
718859
French
Characterization of nicotinami ...
Borreliella burgdorferi, Caenorhabditis elegans, Plasmodium falciparum, Saccharomyces cerevisiae, Streptococcus pneumoniae
Biochemistry
49
10421-10439
2010
-
-
5
-
4
-
46
6
-
-
-
45
-
17
-
-
5
-
-
-
-
-
45
-
-
-
-
6
-
-
-
-
32
-
-
-
-
5
-
-
4
-
-
46
32
6
-
-
-
45
-
-
-
5
-
-
-
-
45
-
-
-
-
6
-
-
-
-
-
5
5
-
-
-
718883
French
High-resolution crystal struct ...
Streptococcus pneumoniae
Biochemistry
49
8803-8812
2010
-
-
1
1
1
-
2
-
-
5
1
1
-
5
-
-
1
-
-
-
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
1
-
-
2
-
-
-
5
1
1
-
-
-
1
-
-
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
718885
Seiner
Kinetics and inhibition of nic ...
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Biochemistry
49
9613-9619
2010
-
-
1
-
1
-
4
4
-
2
-
4
-
162
-
-
1
-
-
-
-
-
4
-
-
-
-
4
1
-
-
-
2
-
-
-
-
1
-
-
1
-
-
4
2
4
-
2
-
4
-
-
-
1
-
-
-
-
4
-
-
-
-
4
1
-
-
-
-
1
1
-
4
4
710862
Fyfe
Specificity and mechanism of A ...
Acinetobacter baumannii
Angew. Chem. Int. Ed. Engl.
48
9176-9179
2009
-
-
-
-
-
-
-
-
-
4
1
2
-
2
-
-
-
1
-
-
-
-
3
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
4
1
2
-
-
-
-
-
-
-
-
3
1
-
-
-
-
-
-
-
-
-
2
2
-
-
-
711827
Vrablik
Nicotinamidase modulation of N ...
Caenorhabditis elegans
Development
136
3637-3646
2009
-
-
1
-
1
-
-
-
1
1
-
1
-
4
-
-
-
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
-
1
1
-
1
-
-
-
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
2
2
-
-
-
679806
Zhang
Characterization of Mycobacter ...
Mycobacterium tuberculosis
FEBS J.
275
753-762
2008
-
1
1
-
9
-
-
-
-
2
1
2
-
3
-
-
1
-
-
-
2
-
2
1
1
-
1
-
1
-
1
-
-
-
-
-
1
1
-
-
9
-
-
-
-
-
-
2
1
2
-
-
-
1
-
-
2
-
2
1
1
-
1
-
1
-
1
-
-
-
-
-
-
-
697513
Chong
Enhanced tolerance against ear ...
Drosophila melanogaster
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Nicotinamidase activity is imp ...
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Brucella abortus nicotinamidas ...
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Mycobacterium smegmatis has tw ...
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Reduced pyrazinamidase activit ...
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Purification, gene cloning, ta ...
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Identification, cloning, and e ...
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Increased nicotinamideadenine ...
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Purification and properties of ...
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Purification and characterizat ...
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NAD metabolism in Vibrio chole ...
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Wintzerith
Purification and characterizat ...
Mus musculus
Biochim. Biophys. Acta
613
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1980
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Fuller
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Determination of nicotinamide ...
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Nicotinamide deamidase from Fl ...
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Foster
Pyridine nucleotide cycle of S ...
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Gillam
Nicotinamide deamidase from ra ...
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Albizati
Active-site studies on rabbit ...
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Tanigawa
Purification and properties of ...
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Pardee
Hyperproduction and purificati ...
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246568
Petrack
Nicotinamide deaminase from ma ...
Oryctolagus cuniculus, Rattus norvegicus
J. Biol. Chem.
240
1725-1730
1965
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246567
Sarma
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Studies on the enzymes involve ...
Aspergillus niger
Biochim. Biophys. Acta
81
311-322
1964
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