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Information on EC 2.7.7.3 - pantetheine-phosphate adenylyltransferase and Organism(s) Pseudomonas aeruginosa
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2.7.7.3 pantetheine-phosphate adenylyltransferaseIUBMB Comments
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.
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Word Map
- 2.7.7.3
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ppats
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penultimate
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dpcoa
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pantothen
- pyrophosphate
-
hexameric
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3\'-dephospho-coa
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nucleotidyltransferase
-
dephosphocoenzyme
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phosphopantothenoylcysteine
- medicine
- drug development
The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
phosphopantetheine adenylyltransferase, 4'-phosphopantetheine adenylyltransferase, pantetheine phosphate adenylyltransferase, pantetheine-phosphate adenylyltransferase, dephospho-coa pyrophosphorylase, enterococcus faecalis ppat, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3'-dephospho-CoA pyrophosphorylase
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-
-
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CoaD
dephospho-CoA pyrophosphorylase
-
-
-
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dephospho-coenzyme A pyrophosphorylase
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-
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pantetheine phosphate adenylyltransferase
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-
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phosphopantetheine adenylyltransferase
PPAT
PPAT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
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-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -, -
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
9026-99-7
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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 + pantetheine 4'-phosphate
diphosphate + 3'-dephospho-CoA
-
-
-
r
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 + pantetheine 4'-phosphate
diphosphate + 3'-dephospho-CoA
-
-
-
r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
activates about 2.5fold, Mg2+ is essential for enzymatic activity of PPAT
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3R)-3-(3-chlorophenyl)-3-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]propanenitrile
-
(3R)-3-(3-chlorophenyl)-3-[(5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)amino]propanenitrile
lead compound as selective, small molecule inhibitor
(3R)-3-(3-chlorophenyl)-3-[(5-methyl-7-oxo-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)amino]propanenitrile
lead compound as selective, small molecule inhibitor
(3R)-3-(3-chlorophenyl)-3-[(7-[[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]amino]-5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]propanenitrile
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(3R)-3-([7-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)amino]-5-methyl-1H-imidazo[4,5-b]pyridin-2-yl]amino)-3-(3-chlorophenyl)propanenitrile
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1-[5-[(2-[[(1R)-1-(3-chlorophenyl)ethyl]amino]-5-methyl-1H-imidazo[4,5-b]pyridin-7-yl)amino]-2,3-dihydro-1H-indol-1-yl]ethan-1-one
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3-[4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-1-(methoxycarbonyl)piperidin-4-yl]propanoic acid
-
CoA
the enzyme is allosteric in nature and regulated by coenzyme A through feedback inhibition, PPAT forms a ternary complex with diphosphate and coenzyme A
methyl (R)-4-(3-(2-cyano-1-((5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino)ethyl)benzyl)piperidine-1-carboxylate
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methyl 4-(2-cyanoethyl)-4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]piperidine-1-carboxylate
-
methyl 4-(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]benzene-1-sulfonyl)piperidine-1-carboxylate
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methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-4-(3-hydroxypropyl)piperidine-1-carboxylate
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methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-4-[(Z)-(methoxyimino)methyl]piperidine-1-carboxylate
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methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-4-[[(2-hydroxyethyl)amino]methyl]piperidine-1-carboxylate
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methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)sulfanyl]piperidine-1-carboxylate
-
additional information
transition of PPAT in Pseudomonas aeruginosa from substrate binding to inhibitory states is triggered by an arginine switch
-
additional information
-
transition of PPAT in Pseudomonas aeruginosa from substrate binding to inhibitory states is triggered by an arginine switch
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
the enzyme is allosteric in nature
-
additional information
additional information
-
the enzyme is allosteric in nature
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000064
(3R)-3-(3-chlorophenyl)-3-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]propanenitrile
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.000064
(3R)-3-(3-chlorophenyl)-3-[(5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)amino]propanenitrile
Pseudomonas aeruginosa
pH not specified in the publication, temperature not specified in the publication
0.000049
(3R)-3-(3-chlorophenyl)-3-[(5-methyl-7-oxo-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)amino]propanenitrile
Pseudomonas aeruginosa
pH not specified in the publication, temperature not specified in the publication
0.0000011
(3R)-3-(3-chlorophenyl)-3-[(7-[[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]amino]-5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]propanenitrile
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.0000043
(3R)-3-([7-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)amino]-5-methyl-1H-imidazo[4,5-b]pyridin-2-yl]amino)-3-(3-chlorophenyl)propanenitrile
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.0000012
1-[5-[(2-[[(1R)-1-(3-chlorophenyl)ethyl]amino]-5-methyl-1H-imidazo[4,5-b]pyridin-7-yl)amino]-2,3-dihydro-1H-indol-1-yl]ethan-1-one
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.0000082
3-[4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-1-(methoxycarbonyl)piperidin-4-yl]propanoic acid
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.0000025
methyl (R)-4-(3-(2-cyano-1-((5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino)ethyl)benzyl)piperidine-1-carboxylate
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.000013
methyl 4-(2-cyanoethyl)-4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]piperidine-1-carboxylate
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.0000024
methyl 4-(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]benzene-1-sulfonyl)piperidine-1-carboxylate
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.00001
methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-4-(3-hydroxypropyl)piperidine-1-carboxylate
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.0000081
methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-4-[(Z)-(methoxyimino)methyl]piperidine-1-carboxylate
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
0.000024
methyl 4-[(3-[(1R)-2-cyano-1-[(5-methyl-1H-imidazo[4,5-b]pyridin-2-yl)amino]ethyl]phenyl)methyl]-4-[[(2-hydroxyethyl)amino]methyl]piperidine-1-carboxylate
Pseudomonas aeruginosa
pH 7.5, temperature not specified in the publication
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
additional information
additional information
the enzyme is allosteric in nature and regulated by coenzyme A through feedback inhibition. Structure-function analysis, and analysis of catalytic, allosteric and inhibitory mechanisms involved in regulation of PPAT. Changes in side chains R90 and D94 are responsible for transition between catalytic and allosteric inhibitory states. Diphosphate binds in close vicinity of ATP and produces a 10 A flip in the adenine ring of coenzyme A moiety. Transition of PPAT in Pseudomonas aeruginosa from substrate binding to inhibitory states is triggered by an arginine switch
additional information
-
the enzyme is allosteric in nature and regulated by coenzyme A through feedback inhibition. Structure-function analysis, and analysis of catalytic, allosteric and inhibitory mechanisms involved in regulation of PPAT. Changes in side chains R90 and D94 are responsible for transition between catalytic and allosteric inhibitory states. Diphosphate binds in close vicinity of ATP and produces a 10 A flip in the adenine ring of coenzyme A moiety. Transition of PPAT in Pseudomonas aeruginosa from substrate binding to inhibitory states is triggered by an arginine switch
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the enzyme exists as monomer, dimer, and/or trimer depending on the pH value at pH 5.8-7.0, SDS-PAGE and gel filtration, overview
additional information
-
the enzyme exists as monomer, dimer, and/or trimer depending on the pH value at pH 5.8-7.0, SDS-PAGE and gel filtration, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
structure of apo-PPAT. Residues R90 and D94 residues act like a gate near the binding cavity to accommodate and stabilize the incoming ligand
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R90A/D94A
in silico mutation, ligand acetyl-CoA fails to maintain its position inside the binding cavity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and ultrafiltration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene coaD, recombinant His-tagged enzyme expression in Escherichia coli strain BL21(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chatterjee, R.; Mondal, A.; Basu, A.; Datta, S.
Transition of phosphopantetheine adenylyltransferase from catalytic to allosteric state is characterized by ternary complex formation in Pseudomonas aeruginosa
Biochim. Biophys. Acta
1864
773-786
2016
Pseudomonas aeruginosa (Q9I6D1), Pseudomonas aeruginosa
Moreau, R.J.; Skepper, C.K.; Appleton, B.A.; Blechschmidt, A.; Balibar, C.J.; Benton, B.M.; Drumm, J.E.; Feng, B.Y.; Geng, M.; Li, C.; Lindvall, M.K.; Lingel, A.; Lu, Y.; Mamo, M.; Mergo, W.; Polyakov, V.; Smith, T.M.; Takeoka, K.; Uehara, K.; Wang, L.; Wei, J.R.; Weiss, A.H.; Xie, L.; Xu, W.; Zhang, Q.; de Vicente, J.
Fragment-based drug discovery of inhibitors of phosphopantetheine adenylyltransferase from Gram-negative bacteria
J. Med. Chem.
61
3309-3324
2018
Escherichia coli (P0A6I6), Escherichia coli, Pseudomonas aeruginosa (Q9I6D1), Pseudomonas aeruginosa
Skepper, C.K.; Moreau, R.J.; Appleton, B.A.; Benton, B.M.; Drumm, J.E.; Feng, B.Y.; Geng, M.; Hu, C.; Li, C.; Lingel, A.; Lu, Y.; Mamo, M.; Mergo, W.; Mostafavi, M.; Rath, C.M.; Steffek, M.; Takeoka, K.T.; Uehara, K.; Wang, L.; Wei, J.R.; Xie, L.; Xu, W.; Zhang, Q.; de Vicente, J.
Discovery and optimization of phosphopantetheine adenylyltransferase inhibitors with Gram-negative antibacterial activity
J. Med. Chem.
61
3325-3349
2018
Escherichia coli (P0A6I6), Pseudomonas aeruginosa (Q9I6D1)
Mondal, A.; Chatterjee, R.; Datta, S.
Umbrella sampling and X-ray crystallographic analysis unveil an Arg-Asp gate facilitating inhibitor binding inside phosphopantetheine adenylyltransferase allosteric cleft
J. Phys. Chem. B
122
1551-1559
2018
Pseudomonas aeruginosa (A0A0X1KGP2), Pseudomonas aeruginosa, Pseudomonas aeruginosa 2192 (A0A0X1KGP2)
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