Information on EC 6.3.2.1 - Pantoate-beta-alanine ligase

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

EC NUMBER
COMMENTARY
6.3.2.1
-
RECOMMENDED NAME
GeneOntology No.
Pantoate-beta-alanine ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate
show the reaction diagram
bi uni uni bi ping pong mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
additional information
-
pantothenate synthetase catalyzes the formation of a pantoyl-adenylate intermediate upon the ordered addition of ATP and pantoate
PATHWAY
KEGG Link
MetaCyc Link
beta-Alanine metabolism
-
Biosynthesis of secondary metabolites
-
Metabolic pathways
-
Pantothenate and CoA biosynthesis
-
phosphopantothenate biosynthesis I
-
SYSTEMATIC NAME
IUBMB Comments
(R)-Pantoate:beta-alanine ligase (AMP-forming)
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D-Pantoate:beta-alanine ligase (AMP-forming)
-
-
-
-
PanC
Q96VJ9
-
panthotenate synthetase
-
-
Pantoate activating enzyme
-
-
-
-
Pantoic-activating enzyme
-
-
-
-
Pantothenate synthetase
-
-
-
-
Pantothenate synthetase
Q9FKB3
-
Pantothenate synthetase
-
-
Pantothenate synthetase
O24035
-
Pantothenate synthetase
O24210
-
Pantothenate synthetase
Q2FV22
-
PS
O24210
-
Synthetase, pantothenate
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9023-49-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
ecotype Columbia-0, single gene
UniProt
Manually annotated by BRENDA team
strain 19
-
-
Manually annotated by BRENDA team
Brucella abortus 19
strain 19
-
-
Manually annotated by BRENDA team
gene panC
-
-
Manually annotated by BRENDA team
IFO 13168
-
-
Manually annotated by BRENDA team
f. sp. lycopersici
SwissProt
Manually annotated by BRENDA team
PanC is essential for growth
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
-
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
P31663
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
-
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-, Q96VJ9
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
O24035
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
O24210
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
Q9FKB3
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
Q2FV22, -
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
last step in pantothenate biosynthesis pathway
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
the enzyme is involved in biosynthesis of the phosphopantetheine moiety
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
synthesis of pantothenate, the essential precursor to coenzyme A
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
Bi Uni Uni Bi kinetic mechanism. Enzyme displays non-allosteric behavior
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-, P0A5R0
the phosphate group of AMP serves as an anchor for the binding of beta-alanine
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
the two-step reaction mechanism, large allosteric effects
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
Brucella abortus 19
-
-
-
-
-
ATP + (R)-pantoate + beta-alanine
?
show the reaction diagram
-
formation of pantothenic acid, an important member of the B vitamins
-
-
-
CTP + (R)-pantoate + beta-alanine
CMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
14% of the activity relative to ATP
-
-
-
GTP + (R)-pantoate + beta-alanine
GMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
12% of the activity relative to ATP
-
-
-
UTP + (R)-pantoate + beta-alanine
UMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
16% of the activity relative to ATP
-
-
-
ITP + (R)-pantoate + beta-alanine
IMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
14% of the activity relative to ATP
-
-
-
additional information
?
-
Q9FKB3
pantothenate synthetase is essential but not limiting for pantothenate biosynthesis in Arabidopsis thaliana, pantothenate, i.e. vitamin B5, is the universal precursor for coenzyme A, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-, Q96VJ9
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
O24035
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
O24210
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
Q9FKB3
-
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
last step in pantothenate biosynthesis pathway
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
the enzyme is involved in biosynthesis of the phosphopantetheine moiety
-
-
?
ATP + (R)-pantoate + beta-alanine
AMP + diphosphate + (R)-pantothenate
show the reaction diagram
-
synthesis of pantothenate, the essential precursor to coenzyme A
-
-
?
ATP + (R)-pantoate + beta-alanine
?
show the reaction diagram
-
formation of pantothenic acid, an important member of the B vitamins
-
-
-
additional information
?
-
Q9FKB3
pantothenate synthetase is essential but not limiting for pantothenate biosynthesis in Arabidopsis thaliana, pantothenate, i.e. vitamin B5, is the universal precursor for coenzyme A, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Co2+
-
maximal activity at 10 mM, slight activation
K+
-
activates; Km: 5.5 mM
K+
-
Km: 5.5 mM
K+
-
combination of divalent and monovalent cation required
Mg2+
-
maximal activity at 10 mM, very strong activation
Mg2+
Q2FV22, -
-
Mg2+
-
divalent cation required, Mg2+ or Mn2+, Km: 2.0 mM. Optimal concentration: 10 mM, inhibition above
Mg2+
-
combination of divalent and monovalent cation required
Mg2+
-
stimulates
Mn2+
-
maximal activity at 10 mM, very strong activation
Mn2+
-
divalent cation required, Mg2+ or Mn2+. Optimal concentration: 5 mM, inhibition above
Mn2+
-
combination of divalent and monovalent cation required; divalent cation required, Mg2+ or Mn2+. Optimal concentration: 5 mM, inhibition above
Mn2+
-
combination of divalent and monovalent cation required
NH4+
-
activates
NH4+
-
combination of divalent and monovalent cation required
Ni2+
-
maximal activity at approx. 3 mM, slight activation
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2RS)-5'-O-(2-hydroxy-4-methoxybutyrylsulfamoyl)adenosine
-
-
(2RS)-5'-O-(3,3-dimethyl-2-aminobutyrylsulfamoyl)adenosine
-
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxy-4-methoxybutyrylsulfamoyl)adenosine
-
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxybutyrylsulfamoyl)adenosine
-
-
(2RS)-5'-O-(3,3-dimethyl-2-oxobutyrylsulfamoyl)adenosine
-
-
(2RS)-adenosyl-2-hydroxy-3,3-dimethylbuyrate
-
-
(2RS)-adenosyl-2-hydroxy-4-methoxybutyrate
-
-
(2RS)-adenosyl-3,3-dimethyl-2-hydroxy-4-methoxybutyrate
-
-
(2S)-adenosyl-2-L-amino-3,3-dimethylbutanoate
-
-
(R)-pantoate
-
substrate inhibition
1,10-phenanthroline
-
-
1-benzofuran-2-carboxylic acid
-
competitive with respect to both ATP and pantoate
2,3-Diaminopropanoate
-
slight
2-hydroxybutanoate
-
slight
2-Hydroxypropanoate
-
slight
2-methyl-5-methoxyindole
-
binding mode with the 2-CH3 group facing the pantoate pocket
3,3-dimethyl-2-oxobutyric acid 5-(6-aminopurin-9-yl)-3,4-dihydroxytetrahydrofuran-2-ylmethyl ester
-
-
3-hydroxybutanoate
-
slight
3-hydroxypropanoate
-
slight
4-(2-{3-[(1E,3E)-hexa-1,3,5-trien-1-yl]phenyl}hydrazinyl)-4-oxobutanoic acid
-
27% inhibition
4-Amino-3-hydroxybutanoate
-
32% inhibition at 1 mM
4-Amino-3-hydroxybutanoate
-
-
4-aminobutanoate
-
27% inhibition at 1 mM
4-aminobutanoate
-
-
4-[(4-[[(5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazol-3-yl)carbonyl]amino]-1H-pyrazol-1-yl)methyl]benzoic acid
-
0.1 mM, 99% inhibition
5-Aminopentanoate
-
slight
5-Aminopentanoate
-
-
5-methoxyindole
-
competitive with respect to ATP
5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxylic acid
-
0.1 mM, 12% inhibition
5-tert-butyl-N-(1-[4-[(2-phenylethyl)carbamoyl]benzyl]-1H-pyrazol-4-yl)-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 78% inhibition
5-tert-butyl-N-1H-pyrazol-4-yl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 43% inhibition
5-tert-butyl-N-pyrazol-4-yl-4,5,6,7-tetrahydrobenzo[d]isoxazole-3-carboxamide derivatives
-
silico molecular design, synthesis, and inhibitory activity, overview
5-tert-butyl-N-[1-(2,4,6-trichlorophenyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 17% inhibition
5-tert-butyl-N-[1-(2,4-difluorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 100% inhibition
5-tert-butyl-N-[1-(2-iodobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 84% inhibition
5-tert-butyl-N-[1-(2-methylbenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 89% inhibition
5-tert-butyl-N-[1-(4-chlorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 98% inhibition
5-tert-butyl-N-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 98% inhibition
5-tert-butyl-N-[1-(naphthalen-2-ylmethyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 97% inhibition
5-tert-butyl-N-[4-carbamoyl-3-(4-methoxybenzyl)isoxazol-5-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 79% inhibition
6-Aminohexanoate
-
slight
anserine
-
slight
Asp
-
uncompetitive
aspartate
-
24% inhibition at 1 mM
carnosine
-
slight
cysteine
-
weak
diphosphate
-
-
Fe2+
-
slight
-
gluconate
-
32% inhibition at 1 mM
glycolate
-
30% inhibition at 1 mM
iodoacetate
-
-
iodoacetate
-
weak
L-cysteate
-
-
L-Val
-
uncompetitive
mercaptoethanol
-
weak
Mercaptoethanolamine
-
weak
Mercaptopurine
-
weak
methyl 4-[(4-[[(5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazol-3-yl)carbonyl]amino]-1H-pyrazol-1-yl)methyl]benzoate
-
0.1 mM, 100% inhibition
methyl 6-amino-4-(benzyloxy)-1H-indole-2-carboxylate
-
69% inhibition
Methylmalonate
-
38% inhibition at 1 mM
Mg2+
-
inhibition above 10 mM
Mn2+
-
inhibition above 5 mM
N-(1-benzyl-1H-pyrazol-4-yl)-5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 100% inhibition
N-(2,5-dibromophenyl)-2-hydroxybenzamide
-
-
N-[1-(2,4-dichlorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 18% inhibition
N-[1-(2-bromobenzyl)-1H-pyrazol-4-yl]-5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 94% inhibition
N-[1-[4-(benzylcarbamoyl)benzyl]-1H-pyrazol-4-yl]-5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
0.1 mM, 82% inhibition
nafronyl oxalate
-
competitive inhibitor
pantothenate
-
product inhibition
pantothenic acid
-
-
Pb2+
-
slight
Taurine
-
52% inhibition at 1 mM
tert-butyl 4-[(4-[[(5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazol-3-yl)carbonyl]amino]-1H-pyrazol-1-yl)methyl]benzoate
-
0.1 mM, 79% inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-, Q96VJ9
PanC expression is induced by alpha-tomatine
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.41
-
(R)-pantoate
-
-
1.45
-
(R)-pantoate
-
25C
0.091
-
ATP
-
-
1.75
-
ATP
-
25C
2.6
-
ATP
-
25C, pH 7.8
0.04
-
beta-Alanine
-
-
0.056
-
beta-Alanine
-
-
0.09
-
beta-Alanine
-
25C, pH 7.8, mutant enzyme K160C
0.15
-
beta-Alanine
-
-
0.27
-
beta-Alanine
-
25C, pH 7.8, wild-type enzyme
0.3
-
beta-Alanine
-
25C, pH 7.8, mutant enzyme Q164A
0.31
-
beta-Alanine
-
25C
0.44
-
beta-Alanine
O24035
25C, pH 8.0, at 20 mM pantoate
0.8
-
beta-Alanine
-
25C, pH 7.8
0.98
-
beta-Alanine
O24035
25C, pH 8.0, at 0.5 mM pantoate
0.063
-
D-pantoate
-
-
0.063
-
D-pantoate
-
beta-alanine
0.13
-
D-pantoate
-
25C, pH 7.8
0.044
-
Pantoate
O24035
25C, pH 8.0
0.063
-
Pantoate
-
-
0.12
-
Pantoate
-
-
50
-
Pantoate
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.039
-
(R)-pantoate
-
25C, pH 8.0, wild-type enzyme
0.81
-
(R)-pantoate
-
25C, pH 8.0, mutant enzyme E132A
1.4
-
(R)-pantoate
-
25C
1.5
-
(R)-pantoate
Q2FV22, -
co-substrate: beta-alanine, pH 8.0, 30C
1.4
-
ATP
-
25C
0.01
-
beta-Alanine
-
25C, pH 7.8, mutant enzyme K160C
0.02
-
beta-Alanine
-
25C, pH 7.8, mutant enzyme Q164A
0.16
-
beta-Alanine
-
25C, pH 8.0, wild-type enzyme
0.59
-
beta-Alanine
-
25C, pH 8.0, mutant enzyme E132A
1.01
-
beta-Alanine
-
25C, pH 7.8, wild-type enzyme
1.4
-
beta-Alanine
-
25C
1.5
-
beta-Alanine
Q2FV22, -
co-substrate: (R)-pantoate, pH 8.0, 30C
3.4
-
beta-Alanine
-
25C, pH 7.8
3.4
-
D-pantoate
-
25C, pH 7.8
0.62
-
Pantoate
O24035
25C, pH 8.0
6.08
-
Pantoate
O24035
25C, pH 8.0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0008
-
(2RS)-5'-O-(2-hydroxy-4-methoxybutyrylsulfamoyl) adenosine
-
25C
0.065
-
(2RS)-5'-O-(3,3-dimethyl-2-aminobutyrylsulfamoyl)adenosine
-
25C
0.16
-
(2RS)-5'-O-(3,3-dimethyl-2-aminobutyrylsulfamoyl)adenosine
-
25C
0.25
-
(2RS)-5'-O-(3,3-dimethyl-2-aminobutyrylsulfamoyl)adenosine
-
25C
0.03
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxy-4-methoxybutyrylsulfamoyl)adenosine
-
25C
0.054
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxy-4-methoxybutyrylsulfamoyl)adenosine
-
25C
0.144
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxy-4-methoxybutyrylsulfamoyl)adenosine
-
25C
0.0003
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxybutyrylsulfamoyl)adenosine
-
25C
0.0008
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxybutyrylsulfamoyl)adenosine
-
25C
0.0011
-
(2RS)-5'-O-(3,3-dimethyl-2-hydroxybutyrylsulfamoyl)adenosine
-
25C
0.014
-
(2RS)-5'-O-(3,3-dimethyl-2-oxobutyrylsulfamoyl)adenosine
-
25C
0.015
-
(2RS)-5'-O-(3,3-dimethyl-2-oxobutyrylsulfamoyl)adenosine
-
25C
0.12
-
(2RS)-5'-O-(3,3-dimethyl-2-oxobutyrylsulfamoyl)adenosine
-
25C
2.5
-
(2RS)-adenosyl-2-hydroxy-3,3-dimethylbuyrate
-
25C
3.5
-
(2RS)-adenosyl-2-hydroxy-4-methoxybutyrate
-
25C
18.2
-
(2RS)-adenosyl-3,3-dimethyl-2-hydroxy-4-methoxybutyrate
-
25C
9.5
-
(2S)-adenosyl-2-L-amino-3,3-dimethylbutanoate
-
25C
1.9
-
3,3-dimethyl-2-oxobutyric acid 5-(6-aminopurin-9-yl)-3,4-dihydroxytetrahydrofuran-2-ylmethyl ester
-
25C
0.075
-
nafronyl oxalate
-
-
4.5
-
pantothenate
-
25C, pH 7.8, vs. beta-alanine
5.7
-
pantothenate
-
25C, pH 7.8, vs. D-pantoate
7.6
-
pantothenate
-
25C, pH 7.8, vs. ATP
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
460
-
4-[(4-[[(5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazol-3-yl)carbonyl]amino]-1H-pyrazol-1-yl)methyl]benzoic acid
-
-
140
-
5-tert-butyl-N-(1-[4-[(2-phenylethyl)carbamoyl]benzyl]-1H-pyrazol-4-yl)-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
61000
-
5-tert-butyl-N-1H-pyrazol-4-yl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
130
-
5-tert-butyl-N-[1-(2,4-difluorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
160
-
5-tert-butyl-N-[1-(2-iodobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
120
-
5-tert-butyl-N-[1-(2-methylbenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
140
-
5-tert-butyl-N-[1-(4-chlorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
150
-
5-tert-butyl-N-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
90
-
5-tert-butyl-N-[1-(naphthalen-2-ylmethyl)-1H-pyrazol-4-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
7130
-
5-tert-butyl-N-[4-carbamoyl-3-(4-methoxybenzyl)isoxazol-5-yl]-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
0.2507
-
actinomycin D
-
pH and temperature not specified in the publication
160
-
methyl 4-[(4-[[(5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazol-3-yl)carbonyl]amino]-1H-pyrazol-1-yl)methyl]benzoate
-
-
0.02244
-
methyl 6-amino-4-(benzyloxy)-1H-indole-2-carboxylate
-
pH and temperature not specified in the publication
97
-
N-(1-benzyl-1H-pyrazol-4-yl)-5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
140
-
N-[1-(2-bromobenzyl)-1H-pyrazol-4-yl]-5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
210
-
N-[1-[4-(benzylcarbamoyl)benzyl]-1H-pyrazol-4-yl]-5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazole-3-carboxamide
-
-
0.3984
-
nafronyl oxalate
-
pH and temperature not specified in the publication
250
-
tert-butyl 4-[(4-[[(5-tert-butyl-4,5,6,7-tetrahydro-1,2-benzisoxazol-3-yl)carbonyl]amino]-1H-pyrazol-1-yl)methyl]benzoate
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1.36
-
O24035
-
2.05
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
-
-
exchange between beta-alanine and pantothenate in the presence of AMP
7.8
-
O24035
in Tris-HCl
8
8.5
-
-
8
-
O24035
in potassium phosphate
8.5
-
Q2FV22, -
-
9
-
-
synthesis of pantothenate
9
-
Q9FKB3
assay at
9
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
9
O24035
50% of maximal activity at pH 7.0, 15% of maximal activity at pH 6.0 and pH 9.0 respectively
7.1
9
O24035
in Tris-HCl, no activity at pH 7.0, 75% of maximal activity at pH 9.0
7.4
9.4
-
7.4: about 40% of maximal activity, 9.4: about 80% of maximal activity
8
12
-
about 50% of maximal activity at pH 8 and 12
8
9
Q2FV22, -
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
Q2FV22, -
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
50
-
20C: about 60% of maximal activity, 50C, about 25% of maximal activity
30
45
-
30C: maximal activity, 37C: 90% of maximal activity, 45C: 60% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q9FKB3
transcript and metabolite patterns of CoA biosynthesis during seed development involving the enzyme, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Brucella melitensis biotype 1 (strain 16M / ATCC 23456 / NCTC 10094)
Burkholderia thailandensis (strain E264 / ATCC 700388 / DSM 13276 / CIP 106301)
Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168)
Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Staphylococcus aureus (strain MRSA252)
Staphylococcus aureus (strain NCTC 8325)
Staphylococcus aureus (strain NCTC 8325)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
65000
-
-
gel filtration
65000
-
-
gel filtration
69000
-
-
gel filtration
70000
-
-
sedimentation equilibrium ultracentrifugation
72800
-
O24035
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
O24210
x * 33900, deduced from nucleotide sequence
?
-, Q96VJ9
x * 43000, SDS-PAGE
?
-
x * 18000, SDS-PAGE in presence of 2-mercaptoethanol
dimer
O24035
2 * 34000, SDS-PAGE
dimer
-
2 * 32677, deduced from nucleotide sequence; 2 * 33000, SDS-PAGE
dimer
-
2 * 31611, mass spectroscopy, crystallization
dimer
-
2 * 30000, SDS-PAGE
dimer
-
molecular dynamics simulations show that the functional dynamics of the enzyme are dominated by motions of a flexible gate loop in the N-terminal domain and of the C-terminal domain. The gate loop motions dominate in Mycobacterium tuberculosis pantothenate synthetase while the C-terminal domain motion dominates in Escherichia coli pantothenate synthetase. Simulations also show that the correlated motions of the domains are severely compromised in the monomeric forms
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structures of pantothenate synthetase complexed with diphosphomethylphosphonic acid adenosyl ester and pantoate resolved at 1.6 A and of apo Escherichia coli pantothenate synthetase resolved at 1.70 A are used as the initial structures for the simulations
-
native and selenomethionine labeled PS, hanging drop vapor diffusion, hanging drops are composed of equal volumes of PS and reservoir solutions consisting of 50 mM Tris-HCl, pH 8.0, 4%-6% polyethylene glycol 4000, crystals appeare at 19C after 2-4 days, crystals diffract to 1.7 A
-
tertiary structure of the dimeric N-terminal domain of Escherichia coli pantothenate synthetase, to a resolution of 1.7 A, shows a second molecule of pantoate bound in the ATP-binding pocket. Pantoate binding to the ATP-binding site induces large changes in structure, mainly for backbone and side chain atoms of residues in the ATP binding HXGH(34-37) motif. ATP stoichiometrically displaces pantoate from the ATP-binding site
-
crystal structure of the enzyme complexed with AMP, ATP or beta-alanine
-
crystal structures of pantothenate synthetase complexed with diphosphomethylphosphonic acid adenosyl ester and pantoate resolved at 1.6 A and of apo Escherichia coli pantothenate synthetase resolved at 1.70 A are used as the initial structures for the simulations
-
crystal structures with compounds 5-methoxyindole and 2-carboxybenzofuranoic acid bound in a ternary complex and in complex with 2-(2-((benzofuran-2-carboxamido)methyl)-5-methoxy-1H-indol-1-yl)acetic acid
-
crystals of native PS and PS complexed with alpha,beta-methyleneadenosine 5'-triphosphate, pantoate and the reaction intermediate pantoyl adenylate, crystals are grown by hanging-drop vapor diffusion, 0.003-0.005 ml of PS solution at 10 mg/ml PS is mixed with an equal volume of well solution, best crystals are obtained with well solutions containing 10%-15% polyethylene glycol 3000, 5% glycerol, 2% ethanol, 20 mM MgCl2, 150 mM Li2SO4 and 100 mM imidazole, pH 8.0 at 20C, crystals diffract to 1.6-2.0 A
-
structures of the apoenzyme and the reaction intermediate complex are determined by X-ray crystallography to resolutions of 2.5 A and 1.85 A, respectively. Structural analysis indicate that the apoenzyme adopts an open and relatively mobile structure, while the complex structure is closed and entirely rigid. In the complex structure, pantothenate synthetase and acetate are bound in the active site. Acetate might mimic the substrate beta-alanine. Therefore, the complex structure might represent a catalytic state poised for in-line nucleophilic attack on pantothenate synthetase
Q2FV22, -
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
11
-
15 min, 40C, stable
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
pH 5.0-10.0, 15 min stable
60
-
-
10 min, complete loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
lyophilized enzyme is very stable
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, stable for 6 months
-
-20C, no loss of activity
O24035
4C, 4 weeks, 25% loss of activity
O24035
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
fusion protein with cytochrome b5
-
partial
-
recombinant His-tagged enzyme
-
recombinant pantothenate synthetase
-
recombinant PanC
-, Q96VJ9
recombinant pantothenate snthetase
O24035
recombinant PanC
-
recombinant pantothenate synthetase
-
using Ni-NTA chromatography
Q2FV22, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli as N-terminal His-tagged protein
-
promoter:beta-glucuronidase analysis
Q9FKB3
expression in Escherichia coli BL21 as N-terminal His-tagged protein
-
gene panC, recombinant expression as His-tagged enzyme, and expression in and complementation of the Arabidopsis thaliana knockout mutant phenotype by heterologous expression of Escherichia coli PTS, the panC transgene increases the total PTS activity in leaves of trangenic plants by up to 500fold but does not affect the steady-state level of pantothenate, overview
-
overexpression as a fusion protein with cytochrome b5 in Escherichia coli BL21(DE3). The advantages of the cytochrome b5 fusion system are its high expression levels in both rich and minimal medium, high solubility, stability, ease of purification, small size, and characteristic color
-
expression in Escherichia coli
-, Q96VJ9
expression Escherichia coli
O24035
expression in Escherichia coli
-
wild-type and mutant enzymes expressed in Escherichia coli BL21
-
-
O24210
expressed in Escherichia coli as a His-tagged fusion protein
Q2FV22, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D63G
-
mutation increases the mobility of the gate loop in Escherichia coli pantothenate synthetase
E77G
-
87% of wild-type activity
G74D
-
mutation reduces the mobility of the gate loop in Mycobacterium tuberculosis pantothenate synthetase
H44A
-
greater than 1000fold reduction in enzyme activity
H47A
-
greater than 1000fold reduction in enzyme activity
K160A
-
greater than 1000fold reduction in enzyme activity
K160C
-
activity is markedly enhanced by the alkylation of cysteine with bromoethylamine
N69A
-
greater than 1000fold reduction in enzyme activity
Q164A
-
mutant exhibits 50fold less activity than wild-type enzyme
Q72A
-
greater than 1000fold reduction in enzyme activity
E132A
-
kcat for beta-alanine is 3.7fold higher than wild-type value, kcat for pantoate is 21fold higher than wild-type value
additional information
Q9FKB3
construction of an uxotrophic AtPTS knockout mutant, phenotype, overview. Complementation of the mutant phenotype by heterologous expression of Escherichia coli PTS gene panC. The panC transgene increases the total PTS activity in leaves by up to 500fold but does not affect the steady-state level of pantothenate. The AtPTS knockout phenotype is rescued by exogenous pantothenate