Information on EC 2.7.7.18 - nicotinate-nucleotide adenylyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.7.7.18
-
RECOMMENDED NAME
GeneOntology No.
nicotinate-nucleotide adenylyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + beta-nicotinate D-ribonucleotide = diphosphate + deamido-NAD+
show the reaction diagram
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nucleotidyl group transfer
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
NAD biosynthesis from 2-amino-3-carboxymuconate semialdehyde
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NAD biosynthesis I (from aspartate)
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NAD metabolism
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NAD salvage pathway I
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NAD salvage pathway II
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Nicotinate and nicotinamide metabolism
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pyridine nucleotide cycling (plants)
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SYSTEMATIC NAME
IUBMB Comments
ATP:nicotinate-ribonucleotide adenylyltransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
9026-98-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
probable
UniProt
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicum
-
-
-
Manually annotated by BRENDA team
tobacco, cv. Samsun or cv. Xanthi
-
-
Manually annotated by BRENDA team
serotype M6
UniProt
Manually annotated by BRENDA team
serotype M6
UniProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 3-acetyl-pyridine-NAD+
?
show the reaction diagram
ATP + 3-pyridinealdehyde-NAD+
?
show the reaction diagram
ATP + beta-nicotinate D-ribonucleotide
diphosphate + deamido-NAD+
show the reaction diagram
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
show the reaction diagram
ATP + nicotinate ribonucleotide
diphosphate + deamido-NAD+
show the reaction diagram
ATP + nicotinic acid mononucleotide
nicotinic acid adenine dinucleotide + diphosphate
show the reaction diagram
ATP + NMN
diphosphate + NAD+
show the reaction diagram
-
-
-
-
r
deoxy-ATP + nicotinamide ribonucleotide
?
show the reaction diagram
deoxy-ATP + nicotinate ribonucleotide
?
show the reaction diagram
nicotinate mononucleotide + ATP
nicotinate adenine dinucleotide + diphosphate
show the reaction diagram
-
PreissHandler-dependent pathway
-
-
?
nicotinic acid mononucleotide + ATP
nicotinic acid adenine dinucleotide + diphosphate
show the reaction diagram
nicotinic acid mononucleotide + ATP
nicotinic acid dinucleotide + diphosphate
show the reaction diagram
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + beta-nicotinate D-ribonucleotide
diphosphate + deamido-NAD+
show the reaction diagram
ATP + nicotinate ribonucleotide
diphosphate + deamido-NAD+
show the reaction diagram
nicotinate mononucleotide + ATP
nicotinate adenine dinucleotide + diphosphate
show the reaction diagram
-
PreissHandler-dependent pathway
-
-
?
nicotinic acid mononucleotide + ATP
nicotinic acid dinucleotide + diphosphate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
KCl
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activation, 25 mM, NAD+-synthesis, not deamido-NAD+-synthesis
NH4Cl
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activation, can substitute for KCl
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4,4'-[cyclohexa-2,5-diene-1,4-diylidenebis[(E)methylylidene(E)diazene-2,1-diyl]]bis[N-(2-chlorophenyl)-4-oxobutanamide]
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4-[2-(anthracen-9-ylmethylidene)hydrazino]-N-(3-chlorophenyl)-4-oxobutanamide
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nicotinic acid adenine dinucleotide
product inhibition
[(2E)-1-[4-[(2-chlorophenyl)amino]-4-oxobutanoyl]-2-(naphthalen-1-ylmethylidene)hydrazino]acetic acid
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.27
3-acetylpyridine-NAD+
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37C, pH 7.5
0.74
3-pyridinealdehyde-NAD+
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37C, pH 7.5
0.0017 - 4
ATP
0.0045 - 0.029
deamido-NAD+
0.083 - 4.2
diphosphate
0.069 - 1.7
NAD+
0.021 - 0.7
nicotinamide mononucleotide
0.043 - 0.4
nicotinamide ribonucleotide
0.025 - 1.3
nicotinate ribonucleotide
0.015
nicotinic acid mononucleotide
-
2.3
NMN
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37C, pH 7.4
0.0304
reduced nicotinamide mononucleotide
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0079
K891-0166
pH 7.5, 37C
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.013
4,4'-[cyclohexa-2,5-diene-1,4-diylidenebis[(E)methylylidene(E)diazene-2,1-diyl]]bis[N-(2-chlorophenyl)-4-oxobutanamide]
Bacillus anthracis
C3L5T6
pH 7.5, 22C
0.025
4-[2-(anthracen-9-ylmethylidene)hydrazino]-N-(3-chlorophenyl)-4-oxobutanamide
Bacillus anthracis
C3L5T6
pH 7.5, 22C
0.015
K891-0166
Streptococcus pyogenes
Q5XDT7
pH 7.5, 37C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0003
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3-acetyl-pyridine-NAD+ as substrate
0.0008
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3-pyridinealdehyde-NAD+ as substrate
0.00133
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Xanthi, callus culture
0.00269
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Samsun, callus culture
0.00358
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Samsun, root
0.004
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NAD+ as substrate
0.024
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deamido-NAD+ as substrate
0.054
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NMN as substrate
0.34
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NAD+ as substrate
1.42
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3-pyridinealdehyde-NAD+ as substrate
2.8
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deamido-NAD+ as substrate
3.82
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3-acetyl-pyridine-NAD+ as substrate
3.85
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deamido-NAD+ as substrate
5
-
NAD+ as substrate
10.1
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ATP as substrate
11.1
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nicotinate ribonucleotide as substrate
11.5
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diphosphate as substrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
cultured from seedlings' roots
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
isoform NMNAT2 localizes to the cis-Golgi and endoplasmic reticulum-Golgi intermediate compartment. It is palmitoylated at two adjacent cysteine residues of its isoform-specific domain and thereby anchored at the cytoplasmic surface
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
ORGANISM
UNIPROT
Bacillus anthracis (strain CDC 684 / NRRL 3495)
Bacillus anthracis (strain CDC 684 / NRRL 3495)
Bacillus anthracis (strain CDC 684 / NRRL 3495)
Bacillus anthracis (strain CDC 684 / NRRL 3495)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Burkholderia thailandensis (strain E264 / ATCC 700388 / DSM 13276 / CIP 106301)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Mycobacterium abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC 1543)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Staphylococcus aureus (strain COL)
Staphylococcus aureus (strain COL)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24350
calculated from amino acid sequence
36370 - 49140
-
gel filtration, sedimentation equlibrium centrifugation
44000
by gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
Methanothermobacter thermautotrophicum
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homohexamer
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homotetramer
monomer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with inhibitors 4-[2-(anthracen-9-ylmethylidene)hydrazino]-N-(3-chlorophenyl)-4-oxobutanamide, 4,4'-[cyclohexa-2,5-diene-1,4-diylidenebis[(E)methylylidene(E)diazene-2,1-diyl]]bis[N-(2-chlorophenyl)-4-oxobutanamide], and [(2E)-1-[4-[(2-chlorophenyl)amino]-4-oxobutanoyl]-2-(naphthalen-1-ylmethylidene)hydrazino]acetic acid. 4-[2-(Anthracen-9-ylmethylidene)hydrazino]-N-(3-chlorophenyl)-4-oxobutanamide binds at an enzyme monomer-monomer interface formed in the crystal of the complex, it sits at a central cleft between strands beta1 and beta4 of the beta sheet, which is the catalytic and substrate binding sites of the enzyme. The structures reveal a common binding site near residues Trp117, Try112, and Met109. This site overlaps but is distinct from the substrate-binding pocket
sitting drop and hanging drop vapour diffusion method, mixing 0.001 ml of 4 mg/ml protein in 50 mM Tris, pH 7.0, 100 mM NaCl, 100 mM Arg, 100 mM Glu, 1% glycerol, 1 mM DTT, and containing 200 mM trehalose, with 0.001 ml of reservoir solution containing 2.1 M ammonium sulfate, 100 mM HEPES pH 7.0, 2% PEG 400 and 10 mM MgCl2, cryoprotection by 25% glycerol, X-ray diffraction structure determination and analysis at 2.3 A resolution, usage molecular replacement and of self-interaction chromatography for process optimization
crystals of the apo-enzyme belong to space group: P21 with 58.5% solvent and contain four molecules of NaMN AT in the asymmetric subunit, crystals in complex with deamido-NAD+ belong to space group: P212121 with 55.6% solvent and contain six molecules of NaMN AT in the asymmetric subunit, conditions: polyethylene glycol 3350 and 100 mM MgCl2
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crystallization of the apo-enzyme to space group: P1 with 44% sovent, and in complex with deamido-NAD+ with 42.4% solvent in space group I222, hanging-drop vapour-diffusion method at 20C in 100 mM Tris, pH 7, 200 mM NaCl and 800 mM sodium citrate
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crystal structure of NaMN-bound form at 1.7 A, ATP-bound form at 2.0 A, apo-form at 2.0 A. The substrate-unbound and substrate-complexed structures are all in the fully open conformation. There is little conformational change upon binding each of the substrates. A conformational change is necessary to bring the two substrates closer together for initiating the catalysis. The authors suggest that such a conformational change likely occurs only after both substrates are simultaneously bound in the active site
Crystals of saNaMNAT were initially obtained at 22C from polyethylene glycol 3000 and phosphatecitrate buffer.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55
-
5 min 54% loss of activity
65
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5 min 65% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
phosphate buffer, 0.08 M, pH 7.5, stabilizes
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0-3C, 22% loss of activity within 31 days
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0-3C, 31 days stable
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frozen 24 h
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
recombinant enzyme
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration to homogeneity
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli NZN111 with IdhA and pflB genes inactivated for the production of succinic acid
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expression in HeLa S3 cells; expression in HeLa S3 cells; expression in HeLa S3 cells
gene nadD, overexpression of the His-tagged enzyme in Escherichia coli strain BL21(DE3)
overexpression in Escherichia coli BL21 with a 6 x His-tag
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overexpression in Escherichia coli BL21 with a His-tag
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
the enzyme is a target for inhibitor development
synthesis
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overexpression of enzyme gene under anaerobic conditions in a strain lacking IdhA and pflB gene products leads to 3.21fold increase in NAD+ and 1.67fold increase in NADH in the recombinant strain. Enzyme expression restores cell growth and glucose utilization under anaerobic conditions. After 72 h, the recombinant strain can consume 14 g/l of lgucose and produce 6.23 g/l of succinic acid
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