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Information on EC 2.7.7.18 - nicotinate-nucleotide adenylyltransferase and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WJJ5
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2.7.7.18 nicotinate-nucleotide adenylyltransferaseSpecify your search results
Word Map
- 2.7.7.18
- anthracis
- falciparum
-
plasmodium
-
salvage
-
adenylylation
-
malaria
-
broad-spectrum
- nadp
-
deamidated
- medicine
- drug development
- analysis
- synthesis
The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
nicotinate mononucleotide adenylyltransferase, nicotinic acid mononucleotide adenylyltransferase, pfnmnat, namn at, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
adenylyltransferase, nicotinate mononucleotide
-
-
-
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deamido-NAD+ pyrophosphorylase
-
-
-
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deamidonicotinamide adenine dinucleotide pyrophosphorylase
-
-
-
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NaMN AT
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-
-
-
NaMN-ATase
-
-
-
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nicotinic acid mononucleotide adenylyltransferase
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:nicotinate-ribonucleotide adenylyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9026-98-6
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + nicotinate beta-D-ribonucleotide
diphosphate + deamido-NAD+
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + nicotinate beta-D-ribonucleotide
diphosphate + deamido-NAD+
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
MIC80 values of 0.02-0.1 mM and above. The compounds show no inhibition of the human enzyme
2-(2,4-dimethylphenyl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
-
2-(2,4-dimethylphenyl)-N-[4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]quinoline-4-carboxamide
-
2-(2-chlorophenyl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
-
2-(4-bromophenyl)-N-[4-[(4-methylpyrimidin-2-yl)sulfamoyl]phenyl]quinoline-4-carboxamide
-
2-(furan-2-yl)-N-[3-(3,4,5,6-tetrahydropyridin-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
-
2-(furan-2-yl)-N-[3-methoxy-4-(morpholin-4-ylsulfonyl)phenyl]quinoline-4-carboxamide
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2-(furan-2-yl)-N-[3-methyl-4-(morpholin-4-ylsulfonyl)phenyl]quinoline-4-carboxamide
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2-(pyridin-4-yl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
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2-phenyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
-
3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]benzamide
-
4-[ethyl(phenyl)sulfamoyl]-N-[5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl]benzamide
-
N-[3-(3,4-dihydro-2H-pyrrol-5-ylsulfamoyl)phenyl]-2-(furan-2-yl)quinoline-4-carboxamide
-
N-[3-[1-(6-chloro-4-phenylquinazolin-2-yl)-5-(furan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl]phenyl]methanesulfonamide
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N-[4-(3,4-dihydro-2H-pyrrol-5-ylsulfamoyl)phenyl]-2-(furan-2-yl)quinoline-4-carboxamide
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N-[4-(4-iodophenyl)-1,3-thiazol-2-yl]-3-[(phenylsulfonyl)amino]benzamide
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N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-3-[(phenylsulfonyl)amino]benzamide
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N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]-3-methylphenyl]-2-(4-methoxyphenyl)quinoline-4-carboxamide
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N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]-3-methylphenyl]-2-(4-methylphenyl)quinoline-4-carboxamide
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S-(4-bromo-8-chloronaphthalen-1-yl) [4-(1,3-thiazol-2-ylsulfamoyl)phenyl]carbamothioate
-
additional information
inhibitory profiling of partially active mutants and wild-type enzyme MtNadD using small molecule inhibitors, overview. Substrate inhibition in an ordered bi-reactant system
-
additional information
-
inhibitory profiling of partially active mutants and wild-type enzyme MtNadD using small molecule inhibitors, overview. Substrate inhibition in an ordered bi-reactant system
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.33
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant Q46A
0.43
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant L164Q
0.48
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant wild-type enzyme
0.52
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant L164A
0.53
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant T12A
0.84
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant P44A
0.98
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W45A
1.13
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W117F
2.67
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W117A
2.7
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant K47A
2.8
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant T86A
additional information
additional information
steady-state kinetic analysis, sequential kinetic mechanism, bisubstrate enzyme kinetics, overview
-
additional information
additional information
-
steady-state kinetic analysis, sequential kinetic mechanism, bisubstrate enzyme kinetics, overview
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W117A
0.015
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant L164Q
0.02
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant K47A
0.03
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W117F
0.13
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant L164A
0.2
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant T86A
0.22
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant T12A
0.36
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant P44A
0.37
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W45A
4.7
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant Q46A
5.5
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant wild-type enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0008
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W117A
0.007
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant K47A
0.03
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W117F
0.04
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant L164Q
0.07
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant T86A
0.4
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant P44A
0.4
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant T12A
0.4
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant W45A
2.5
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant L164A
12
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant wild-type enzyme
14
nicotinate beta-D-ribonucleotide
pH 7.5, 37°C, recombinant mutant Q46A
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.024 - 0.114
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
0.024
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant mutant T12A
0.03
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant mutant W117A
0.035
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant wild-type enzyme
0.037
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant mutant P44A
0.056
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant mutant W45A
0.094
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant mutant K47A
0.114
2-(2,4-dimethylphenyl)-N-(4-([(5-methyl-3-isoxazolyl)amino]sulfonyl)phenyl)-4-quinolinecarboxamide
pH 7.5, 37°C, recombinant mutant T86A
additional information
additional information
inhibition kinetics, overview
-
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.036
2-(2,4-dimethylphenyl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.035
2-(2,4-dimethylphenyl)-N-[4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.033
2-(2-chlorophenyl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.049
2-(4-bromophenyl)-N-[4-[(4-methylpyrimidin-2-yl)sulfamoyl]phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.017
2-(furan-2-yl)-N-[3-(3,4,5,6-tetrahydropyridin-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.074
2-(furan-2-yl)-N-[3-methoxy-4-(morpholin-4-ylsulfonyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.051
2-(furan-2-yl)-N-[3-methyl-4-(morpholin-4-ylsulfonyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.056
2-(pyridin-4-yl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.043
2-phenyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.024
3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]benzamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.096
4-[ethyl(phenyl)sulfamoyl]-N-[5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl]benzamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.049
N-[3-(3,4-dihydro-2H-pyrrol-5-ylsulfamoyl)phenyl]-2-(furan-2-yl)quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.13
N-[3-[1-(6-chloro-4-phenylquinazolin-2-yl)-5-(furan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl]phenyl]methanesulfonamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.046
N-[4-(3,4-dihydro-2H-pyrrol-5-ylsulfamoyl)phenyl]-2-(furan-2-yl)quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.18
N-[4-(4-iodophenyl)-1,3-thiazol-2-yl]-3-[(phenylsulfonyl)amino]benzamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.116
N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-3-[(phenylsulfonyl)amino]benzamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.13
N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]-3-methylphenyl]-2-(4-methoxyphenyl)quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
0.13
N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]-3-methylphenyl]-2-(4-methylphenyl)quinoline-4-carboxamide
Mycobacterium tuberculosis
pH 7.5, 37°C, recombinant wild-type enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
nicotinate mononucleotide adenylyltransferase NadD is an essential enzyme in the biosynthesis of the NAD+ cofactor
additional information
additional information
the enzyme has a unique 310 helix that locks the active site in an over-closed conformation. This renders the enzyme inactive as it is topologically incompatible with substrate binding and catalysis. The enzyme contains the signature motifs GXFXPX(H/T)XXH and SXTXXR mainly implicated in ATP binding. Mechanistic modelling, overview
additional information
-
the enzyme has a unique 310 helix that locks the active site in an over-closed conformation. This renders the enzyme inactive as it is topologically incompatible with substrate binding and catalysis. The enzyme contains the signature motifs GXFXPX(H/T)XXH and SXTXXR mainly implicated in ATP binding. Mechanistic modelling, overview
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
three-dimensional structure enzyme structure determination and analysis, crystal structure analysis
additional information
-
three-dimensional structure enzyme structure determination and analysis, crystal structure analysis
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant wild-type and W117A mutant enzymes, sitting drop vapour diffusion method at 20°C, microcrystal seeding using hanging drops, mixing of 10 mg/ml protein in 20 mM Tris, pH 7.8, 200 mM NaCl, and 5% v/v glycerol with well solution containing 1.2-1.5 M MgSO4, 0.1 M MES buffer, pH 6.0-6.5, microseeds are added to the drops 1 h later, macrocrystals growth within 3-5 days., X-ray diffraction structure determination and analysis at 2.4 A resolution, molecular replacement
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K47A
site-directed mutagenesis, the mutant shows a decrease in Km for ATP and a 6fold increase in Km for nicotinate beta-D-ribonucleotide and a nearly abolished enzyme activity
L164A
site-directed mutagenesis, the L164A mutant elutes as both a monomer and a dimer during purification, the mutant shows 40fold reduced activity compared to the wild-type enzyme
L164Q
site-directed mutagenesis, the L164Q mutant elutes as both a monomer and a dimer during purification, almost inactive mutant
P44A
site-directed mutagenesis, the mutant shows a decrease in Km for ATP
T12A
site-directed mutagenesis, the T12A mutant elutes as a dimer and as an aggregated protein during purification, the mutant shows highly reduced activity compared to the wild-type enzyme
T86A
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
W117A
site-directed mutagenesis, the mutant shows a 10fold higher expression level compared to the wild-type enzyme in Escherichia coli, three-dimensional structure determination and analysis, the mutant shows highly reduced activity compared to the wild-type enzyme
W117F
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage from wild-type enzyme and W117A mutant enzyme through Ulp1 protease or TEV protease, and anion exchange chromatography and dialysis
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene nadD, sequence comparisons, recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
enzyme NadD is a potentially druggable target suitable for the development of selective inhibitors
medicine
the enzyme is a target for developing antimycobacterial therapies
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rodionova, I.A.; Zuccola, H.J.; Sorci, L.; Aleshin, A.E.; Kazanov, M.D.; Ma, C.T.; Sergienko, E.; Rubin, E.J.; Locher, C.P.; Osterman, A.L.
Mycobacterial nicotinate mononucleotide adenylyltransferase: structure, mechanism, and implications for drug discovery
J. Biol. Chem.
290
7693-7706
2015
Mycobacterium tuberculosis (P9WJJ5), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WJJ5)
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