Information on EC 2.7.7.3 - pantetheine-phosphate adenylyltransferase

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

EC NUMBER
COMMENTARY hide
2.7.7.3
-
RECOMMENDED NAME
GeneOntology No.
pantetheine-phosphate adenylyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + pantetheine 4'-phosphate = diphosphate + 3'-dephospho-CoA
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
adenosyl group transfer
-
-
nucleotidyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
coenzyme A biosynthesis I (prokaryotic)
-
-
coenzyme A biosynthesis II (eukaryotic)
-
-
Metabolic pathways
-
-
Pantothenate and CoA biosynthesis
-
-
coenzyme A metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:pantetheine-4'-phosphate adenylyltransferase
The enzyme from several bacteria (e.g. Escherichia coli, Bacillus subtilis and Haemophilus influenzae) has been shown to be bifunctional and also to possess the activity of EC 2.3.1.157, glucosamine-1-phosphate N-acetyltransferase.
CAS REGISTRY NUMBER
COMMENTARY hide
9026-99-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
strain CD36; gene coaD
UniProt
Manually annotated by BRENDA team
strain CD36; gene coaD
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene coaD
-
-
Manually annotated by BRENDA team
gene coaD
-
-
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain Rv2965c
-
-
Manually annotated by BRENDA team
no activity in Plasmodium lophurae
avian malaria parasite
-
-
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
UniProt
Manually annotated by BRENDA team
gene coaD
-
-
Manually annotated by BRENDA team
gene coaD
-
-
Manually annotated by BRENDA team
strain HB8
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-deoxy-ATP + pantetheine 4'-phosphate
?
show the reaction diagram
-
phosphorylation at 27% the rate of ATP
-
-
?
4'-phosphopantetheine + ATP
3'-dephospho-CoA + diphosphate
show the reaction diagram
4'-phosphopantetheine + Mg2+-ATP
3'-dephospho-CoA + diphosphate
show the reaction diagram
-
PPAT does not accept 4'-phosphopantothenoyl-Cys as a substrate
-
-
r
ATP + 4'-phosphopantetheine
diphosphate + 3'-dephospho-CoA
show the reaction diagram
-
-
-
r
ATP + pantetheine 4'-phosphate
diphosphate + 3'-dephospho-CoA
show the reaction diagram
diphosphate + 3'-dephospho-CoA
ATP + pantetheine 4'-phosphate
show the reaction diagram
phosphopantetheine + Mg-ATP
dephospho-CoA + diphosphate
show the reaction diagram
phosphopantetheine + MgATP2- + 4 H+
dephospho-CoA + diphosphate + Mg2+
show the reaction diagram
-
coenzyme A (CoA) biosynthesis
-
-
?
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
4'-phosphopantetheine + ATP
3'-dephospho-CoA + diphosphate
show the reaction diagram
ATP + pantetheine 4'-phosphate
diphosphate + 3'-dephospho-CoA
show the reaction diagram
phosphopantetheine + Mg-ATP
dephospho-CoA + diphosphate
show the reaction diagram
-
essential hexameric enzyme that catalyzes the penultimate step in coenzyme A biosynthesis
-
-
r
phosphopantetheine + MgATP2- + 4 H+
dephospho-CoA + diphosphate + Mg2+
show the reaction diagram
-
coenzyme A (CoA) biosynthesis
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
activates, 90% activity compared to Mg2+
Mn2+
activates, 80% activity compared to Mg2+
Zn2+
activates, 70% activity compared to Mg2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1S,2S)-N-(3,4-dichlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
(1S,2S)-N-(3-chlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
2'-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6'-ethyl-4-hydroxy-6-oxo-1,6-dihydro-2,4'-bipyrimidine-5-carboxamide
2-[(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)sulfanyl]-1H-imidazole-5-carboxylic acid
3'-Dephospho-CoA
-
-
3-[3-(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)-1,2,4-oxadiazol-5-yl]propanoic acid
AC1LDVWJ
-
-
-
acetyl-CoA
allosteric inhibitor
adenosine-5'-[(alpha,beta)-methyleno]triphosphate
-
-
coenzyme A
D-amethopterin
-
a mixed-type inhibitor of HpPPAT activity, that simultaneously occupies the HpPPAT 4'-phosphopantetheine- and ATP-binding sites, the compound can serve as a lead compound in drug development, steady-state kinetic inhibition assay. Model of HpPPAT complexed with D-amethopterin, overview
deoxycholate
-
inactivation at 0.2%, activation at 0.01%
dephospho-CoA
-
-
diphosphate
-
-
Omeprazole
-
-
pantetheine
-
potent inhibitor
phosphopantetheine
-
-
PTX040334
PTX042695
T5568746
-
-
-
zanamivir
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cysteine
deoxycholate
-
stimulation at 0.01%, inactivation at 0.2%
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0067 - 0.0147
3'-Dephospho-CoA
0.1157 - 1
ATP
0.017
dephospho-CoA
-
; reverse reaction
0.022 - 0.272
diphosphate
0.22
Mg-ATP
-
forward reaction
0.015 - 0.19
pantetheine 4'-phosphate
0.0047
phosphopantetheine
-
; forward reaction
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000917 - 4.808
3'-Dephospho-CoA
4.547
ATP
Mycobacterium tuberculosis
-
at 25°C in 75 mM HEPES (pH 7.0)
4.853
pantetheine 4'-phosphate
Mycobacterium tuberculosis
-
at 25°C in 75 mM HEPES (pH 7.0)
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0084
acetyl-CoA
pH 7.0, 5°C, recombinant enzyme
0.388
adenosine-5'-[(alpha,beta)-methyleno]triphosphate
-
at 25°C in 75 mM HEPES (pH 7.0)
0.011 - 0.117
CoA
0.2674
D-amethopterin
-
pH 7.9, 25°C, recombinant enzyme
0.121 - 0.192
dephospho-CoA
0.12
diphosphate
-
Substrate: ATP, Cosubstrate: phosphopantetheine (300 microM)
0.0084 - 0.131
phosphopantetheine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00033 - 0.005
(1S,2S)-N-(3,4-dichlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
0.000098 - 0.0088
(1S,2S)-N-(3-chlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
0.000000065 - 0.024
2'-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6'-ethyl-4-hydroxy-6-oxo-1,6-dihydro-2,4'-bipyrimidine-5-carboxamide
0.00004 - 0.0095
2-[(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)sulfanyl]-1H-imidazole-5-carboxylic acid
0.00000013 - 0.2
3-[3-(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)-1,2,4-oxadiazol-5-yl]propanoic acid
0.038
CoA
Arabidopsis thaliana
-
-
0.03
PTX040334
Escherichia coli
-
IC50: 0.03 mM
0.000006
PTX042695
Escherichia coli
-
IC50: 0.000006 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.07
reverse reaction using the purified His-tag fusion protein
7.61
-
-
9.1
-
recombinant enzyme
22.3
-
wild-type enzyme
300
-
diphosphate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
-
7.9
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
41
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.75
-
chromatofocusing technique with a PBE 94 column and Polybuffer 74
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
normal and Plasmodium lophurae-infected
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Acinetobacter baumannii (strain SDF)
Acinetobacter baumannii (strain SDF)
Archaeoglobus fulgidus (strain ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126)
Bacillus subtilis (strain 168)
Burkholderia pseudomallei (strain 1710b)
Burkholderia pseudomallei (strain 1710b)
Coxiella burnetii (strain RSA 493 / Nine Mile phase I)
Enterococcus faecalis (strain ATCC 700802 / V583)
Enterococcus faecalis (strain ATCC 700802 / V583)
Enterococcus faecalis (strain ATCC 700802 / V583)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
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 LESB58)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
17700
-
6 * 17700, crystal structure analysis, analytical ultracentrifugation data of the native enzyme suggests an equilibrium of two trimers and one hexamer in solution
19701
-
6 * 19701, MALDI-TOF mass spectrometry
19990
MALDI-TOF mass spectrometry of His-tag fusion protein
19992
1 * 20000, SDS-PAGE of His-tag fusion protein, circular dichroism, and 2D NMR experiments, 1 * 19992, MALDI-TOF mass spectrometry
35400
-
alpha3, 3 * 35400, SDS-PAGE
57000
-
alpha2, 2 * 57000, SDS-PAGE
61000
-
alpha2, 2 * 61000, SDS-PAGE, subunit structure
62000
gel filtration
67000
-
analytical ultracentrifugation
71000
-
gel filtration
108000
115000
-
gel filtration
118000
-
gel filtration
120000
-
dynamic light-scattering analysis
128600
-
analytical ultracentrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
homohexamer
monomer
trimer
-
alpha3, 3 * 35400, SDS-PAGE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 0.2 M ammonium sulfate, 0.1 M sodium acetate pH 4.6, 30% (w/v) PEG 2000
ligand-unbound state and in complex with ATP and pantetheine, using 3.5 M sodium formate and 100 mM Tris-HCl (pH 8.5)
-
The best crystals are grown with a reservoir solution consisting of 0.1 M sodium HEPES pH 7.5, 0.8 M sodium dihydrogen phosphate, and 0.8 M potassium dihydrogen phosphate. Tetragonal bipyramidal crystals grew to approximate dimensions of 0.1 x 0.1 x 0.1 mm within a few days.
-
at pH 5.0, 100 mM sodium acetate, pH 5.0, 1.1 M ammonium sulfate, 200 mM NaCl
-
co-crystallization with CoA, space group: I23, with a dimer in the asymmetric unit, a solvent content of 0.57 and a volume-to-protein mass ratio of 288 A3 Da-1
-
co-crystallization with inhibitor PTX040334 in 5% DMSO, 22-32% polyethylene glycol 8000, 200 mM ammonium sulfate in 100 mM cacodylate buffer, pH 6-6.5 at 21°C
-
co-crystallization with pantetheine 4'-phosphate or ATP, space group: I23, with a dimer in the asymmetric unit, a solvent content of 57% and a volume-to-protein mass ratio of 288 A3 Da-1
-
hanging drop vapor diffusion method, using 0.1 M Tris–HCl, pH 7.0, containing 2.0 M (NH4)2SO4 and 0.2 M Li2SO4
-
hanging-drop vapour-diffusion method, using sodium chloride as precipitant, trigonal space group P3121 or P3221 with six monomers in the asymmetric unit, a solvent content of 49% and a volume-to-protein mass ratio of 2.39 A3 Da-1
-
mutant enzyme I4V/N76Y
-
apo form and in complex with ATP, counter-diffusion method, using 40 mM cacodylate buffer pH 5.5 containing 10 mM MgCl2, 0.15 mM NaCl, 20 mM cobalt hexamine and 15% (w/v) 2-methyl-2,4-pentanediol as precipitant solution
-
enzyme crystals are grown in microgravity by the capillary counter-diffusion method through a gel layer, mixing of 10 mg/ml protein in 10 mM HEPES, pH 8.0, 0.15 M NaCl, and 14 mM ATP, with reservoir solution containing 0.1 M NaAc, pH 5.0, 10 mM MgCl2, 5 mM HEPES, pH 8.0, 0.075 M NaCl, 14 mM ATP, and 1.1 M ammonium sulfate, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement method
-
enzyme in complex with pantetheine 4'-phosphate and adenosine-5'-[(alpha,beta)-methyleno]triphosphate, sitting drop vapor diffusion method, using 38% (v/v) polyethylene glycol 200 and 0.1 M HEPES (pH 7.2), at 21°C
-
hanging drop vapor diffusion method
-
in complex with coenzyme A, hanging drop vapor diffusion method, using 0.1 M Tris base pH 8.0 and 0.15 M magnesium formate
-
purified recombinant His-tagged enzyme in complex with diphosphate, substrate analogue AMPPNP, and inhibitors acetyl-CoA and CoA, sitting drop vapor diffusion method, mixing of 0.002 ml of protein in 25 mM HEPES, pH 7.0, 300 mM NaCl, and 2% glycerol, with 0.002 ml of well solution containing 17-19% PEG 4000, 0.1 M HEPES, pH 6.8-7.2, 200-350 mM Na-acetate, and 5-7% 2-propanol, 3-4 weeks, 42°C, method optimization, crystals are soaked in 0.1 mM ligand solution, X-ray diffraction structure determination and analysis at 2.2-2.5 A resolution
enzyme from Staphylococcus aureus subsp. aureus MW2 in complex with inhibitors, vapour diffusion method, mixing of 0.0025 ml of protein solution with 0.0025 ml of reservoir solution containing 14% to 19% PEG 3350, 200 mM ammonium sulfate, and 0.1 M propionic acid cacodylate Bis-Tris propane buffer, pH 7.5, 20°C, 5-7 days, X-ray diffraction structure determination and analysis at 1.72-2.38 A resolution, molecular replacement and modelling of inhibitor binding
hanging-drop vapour-diffusion method, 23.85°C
oil batch method
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
-
2 min, inactivation at 46°C
643176
6.7
-
t1/2: 2 min at 46°C
643176
10
-
2 min, 10% loss of activity at 46°C
643176
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
2 min, partial inactivation
46
-
t1/2: 2 min at pH 6.7, pH 10: 10% loss of activity, pH 5.5: 2 min, inactivation
50
-
2 min, inactivation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 0.5 mg protein/ml, at least 1 month
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Co2 + affinity column chromatography
-
copurification as hexamer with 0.5 equivalents of CoA tightly bound per PPAT monomer
-
His Trap column chromatography, and Superdex 200 gel filtration
Ni-nitrilotriacetic acid-agarose affinity chromatography, gel filtration
Ni-NTA agarose column chromatography and Superdex 200 gel filtration
-
partial
Q Sepharose XL resin column chromatography, Q Sepharose HP resin column chromatography, and Sepharose S-200 gel filtration
-
recombinant enzyme PPAT from Escherichia coli strain BL21(DE3) to over 95% purity
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and ultrafiltration
recombinant protein using His-tag
recombinant wild-type and mutant PPAT enzymes from Escherichia coli strain BL21 pLysS(DE3) to over 95% purity
recombinant wild-type and mutant PPAT enzymes from Escherichia coli strain BL21(DE3) to over 90% purity
the fusion protein was purified by amylose affinity chromatography
-
to homogenity
wild-type and recombinant enzyme to homogenity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21 (DE3)
-
expressed in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3)R3 Rosetta cells
expressed in Escherichia coli ER2566 cells
-
expression in Escherichia coli BL21
expression of His6-tagged and wild-type PPAT in Escherichia coli BL21(DE3)
-
expression of native gene in Escherichia coli BL21(DE3) not possible, expression of optimized gene in Escherichia coli BL21(DE3) as His-tag fusion protein
expression of recombinant MBP-PPAT was induced with 1 mM isopropylthio-beta-galactoside in Escherichia coli DH5alpha cells
-
gene coaD, recombinant expression in Escherichia coli strain BL21(DE3)
gene coaD, recombinant His-tagged enzyme expression in Escherichia coli strain BL21(DE3)
gene coaD, recombinant overexpression in Escherichia coli strain BL21(DE3)
gene coaD, recombinant overexpression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
gene coaD, recombinant overexpression of wild/type and mutant enzymes in Escherichia coli strain BL21 pLysS(DE3), overexpression of Streptococcus pneumoniae coaD in Streptococcus pneumoniae is achieved by driving expression from the galU promoter
His-tag, expressed in Escherichia coli
overexpression in Escherichia coli
overexpression in Escherichia coli JM101
-
recombinant expression in Escherichia coli strain BL21(DE3)
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R106A
-
pantothenate kinase (PanK) mutant
I4V/N76Y
-
the mutant is a homotetramer. Despite structural differences between wild type enzyme and IV4/N76Y, they have similar ligand-binding properties
N106H
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
N106Y
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
V136F
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
N106H
-
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
-
N106Y
-
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
-
V136F
-
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
-
F8L
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
N107H
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
T117N
the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
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