Information on EC 6.3.2.5 - phosphopantothenate-cysteine ligase

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

EC NUMBER
COMMENTARY
6.3.2.5
-
RECOMMENDED NAME
GeneOntology No.
phosphopantothenate-cysteine ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
cysteine can be replaced by some of its derivatives
-
-
-
CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
ping pong mechanism
-
CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
mechanism
-
CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
bi uni uni bi ping pong mechanism, with the nucleotide CTP binding first and CMP released last
-
CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
bi uni uni bi ping pong mechanism. 18O from [carboxyl-18O] phosphopantothenate is incorporated into the AMP or CMP produced during PPCS catalysis, consistent with the formation of a phosphopantothenoyl cytidylate or phosphopantothenoyl adenylate intermediate, supporting similar catalytic mechanisms under both CTP and ATP conditions
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
coenzyme A biosynthesis
-
Metabolic pathways
-
Pantothenate and CoA biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
(R)-4'-phosphopantothenate:L-cysteine ligase
Cysteine can be replaced by some of its derivatives.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4-phosphopantothenoylcysteine synthetase
-
-
-
-
CoaB
-
-
-
-
coupling enzyme
-
-
-
-
pantothenate 4-phosphate:L-cysteine ligase
-
-
-
-
phosphopantothenoyl-cysteine ligase
-
-
-
-
phosphopantothenoylcysteine synthetase
-
-
-
-
phosphopantothenoylcysteine synthetase
-
-
phosphopantothenoylcysteine synthetase
-
-
PPC synthase
-
-
-
-
PPC synthetase
-
the bifunctional protein Dfp from Escherichia coli harbors the activity of phosphopantothenoylcysteine synthetase and phosphopantothenoylcysteine decarboxylase
synthetase, phosphopantothenoylcysteine
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9023-50-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
single gene coaBC encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4-phosphopantothenate to 4-phosphopantetheine
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
no activity in Lactobacillus arabinosus
-
-
-
Manually annotated by BRENDA team
no activity in Lactobacillus helveticus
-
-
-
Manually annotated by BRENDA team
no activity in Saccharomyces cerevisiae
-
-
-
Manually annotated by BRENDA team
single gene coaBC encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4-phosphopantothenate to 4-phosphopantetheine
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
gene coaBC is essential, but Escherichia coli can effectively metabolize pantethine to bypass the requirement for coaBC
physiological function
-
gene coaBC is essential. Contrary to Escherichia coli, Pseudomonas aeruginosa cannot metabolize pantethine to bypass the requirement for coaBC
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)-4'-phosphopantothenate + 2-aminoethanethiol disulfide
?
show the reaction diagram
-
-
-
-
?
ATP + (R)-4'-phosphopantothenate + 2-aminoethanethiol disulfide
?
show the reaction diagram
-
10% of activity compared to L-Cys
-
-
?
ATP + (R)-4'-phosphopantothenate + 2-methylcysteine
N-(phosphopantothenyl)-alpha-methylcysteine + ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + (R)-4'-phosphopantothenate + 2-methylcysteine
N-(phosphopantothenyl)-alpha-methylcysteine + ADP + phosphate
show the reaction diagram
-
10% of the activity compared to L-cysteine
-
?
ATP + (R)-4'-phosphopantothenate + beta-mercaptoethylamine
phosphopantetheine + ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + (R)-4'-phosphopantothenate + beta-mercaptoethylamine
phosphopantetheine + ADP + phosphate
show the reaction diagram
-
25% of activity compared to L-Cys
-
?
ATP + (R)-4'-phosphopantothenate + cystine
(R)-4'-phosphopantothenoyl-L-cystine + ADP + phosphate
show the reaction diagram
-
5% of activity compared to L-Cys
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
mammalian enzyme differs from the bacterial enzyme in that it can use any of the other nucleotide triphosphates equally as well as CTP
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
8% of the activity with CTP
-
-
?
ATP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + ADP + phosphate
show the reaction diagram
-
human enzyme can use both ATP and CTP with similar affinity. Catalysis under CTP conditions displays Michaelis-Menten kinetics
-
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
-
-
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
-
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
-
-
-
-
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
CTP specifically required
-
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
CTP specifically required
-
-
-
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
CTP specifically required
-
-
r
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
CTP specifically required
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
mammalian enzyme differs from the bacterial enzyme in that it can use any of the other nucleotide triphosphates equally as well as CTP
-
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
(R)-4'-phosphopantothenoyl-L-cysteine + CDP + phosphate
show the reaction diagram
-
human enzyme can use both ATP and CTP with similar affinity. Enzyme shows cooperative binding of ATP, measured as a Hill constant of 1.7
-
-
?
CTP + (R)-4'-phosphopantothenate + L-Cys
?
show the reaction diagram
-
Browns pathway of CoA synthesis
-
-
?
CTP + (R)-4'-phosphopantothenate + L-cysteine
CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
-
-
-
-
?
CTP + (R)-4'-phosphopantothenate + L-cysteine
CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
-
detection of the 4'-phosphopantothenoyl-CMP intermediate
-
-
?
CTP + (R)-4'-phosphopantothenate + L-cysteine
CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
-
the enzyme is required for various processes that occur during oogenesis including chorion patterning, e.g. for F-actin remodeling during cytoplasmic dumping, 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
CTP + (R)-4'-phosphopantothenate + L-Cys
?
show the reaction diagram
-
Browns pathway of CoA synthesis
-
-
?
CTP + (R)-4'-phosphopantothenate + L-cysteine
CMP + diphosphate + N-[(R)-4'-phosphopantothenoyl]-L-cysteine
show the reaction diagram
-
the enzyme is required for various processes that occur during oogenesis including chorion patterning, e.g. for F-actin remodeling during cytoplasmic dumping, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
required
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
CMP
-
competitive to CTP, mixed type to (R)-4'-phosphopantothenate, uncompetitive to L-Cys
phosphate
-
at 10 mM
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.013
-
(R)-4'-phosphopantothenate
-
co-substrate ATP, pH 7.6, 37C
-
0.017
-
(R)-4'-phosphopantothenate
-
pH 7.6, 37C
-
0.057
-
(R)-4'-phosphopantothenate
-
co-substrate CTP, pH 7.6, 37C
-
0.78
-
(R)-4'-phosphopantothenoyl-L-cysteine
-
pH 7.6
0.071
0.083
4'-phosphopantothenate
-
37C, pH 7.5
0.29
-
4'-phosphopantothenate
-
pH 7.6
0.269
-
ATP
-
pH 7.6, 37C
0.156
-
CTP
-
pH 7.6, 37C
0.265
-
CTP
-
pH 7.6, 37C
0.29
-
CTP
-
pH 7.6
0.24
-
cysteine
-
pH 7.6
0.014
-
L-Cys
-
co-substrate ATP, pH 7.6, 37C
0.016
-
L-Cys
-
co-substrate CTP, pH 7.6, 37C
0.086
-
L-Cys
-
pH 7.6, 37C
additional information
-
additional information
-
enzyme shows cooperative binding of ATP, measured as a Hill constant of 1.7
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.56
-
ATP
-
pH 7.6, 37C
0.53
-
CTP
-
pH 7.6, 37C
2.9
-
CTP
-
pH 7.6, 37C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.7
-
AMP
-
pH 7.6, 37C
0.465
-
ATP
-
pH 7.6, 37C
4.69
-
CMP
-
pH 7.6, 37C
0.074
-
CTP
-
pH 7.6, 37C
0.372
-
GTP
-
pH 7.6, 37C
0.766
-
L-Cys
-
substrate CTP, pH 7.6, 37C
0.662
-
UTP
-
pH 7.6, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
normal and infected with Plasmodium lophurae
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
42000
-
-
gel filtration
60000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
two identical subunits, crystallization data
dimer
-
2 * 26100, SDS-PAGE
dimer
-
2 * 28415, ESI-MS
additional information
-
enzyme is part of the Dfp flavoprotein
additional information
-
enzymic activity lies within the C-terminal domain of Dfp protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
structure of the C-terminal recombinant fragment of Escherichia coli Dfp protein spanning Ser181 to Arg406 which harbors the structures of the phosphopantothenoylcysteine synthetase, apo-form and the synthetase complexed with CTP, the activated acyl-intermediate, 4'-phosphopantothenoyl-CMP and with the reaction product CMP, sitting drop vapor diffusion
P0ABQ0
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme
-
purified as His tag protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expression in Escherichia coli
-
overexpression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A275T
-
temperature sensitive mutant dfp-1
A275V
-
unable to form dimers
D203N
-
unable to form dimers
K289Q
-
complete loss of enzymic activity
N210D
-
complete loss of enzymic activity, but intermediate 4-phosphopanthotenoyl-CMP is formed
N210H
-
used for isolation of reaction intermediate
N210K
-
used for isolation of reaction intermediate
T194V
-
unable to form dimers
T198V
-
unable to form dimers
K310Q
-
very low activity
N217H
-
mutant enzyme has residual activity
additional information
-
mutation in dPPCS impair female fecundity and fertility, and disrupts the organization of the somatic and germ line cells, affects F-actin organization and results in abnormal PtdIns(4,5)P2 localization. Improper cell organization coincides with aberrant localization of the membrane molecules Gurken (Grk) and Notch, whose activities are required for specification of the follicle cells that pattern the eggshell. Mutations in dPPCS also induce alterations in scutellar patterning and cause wing vein abnormalities, phenotype, detailed overview