Information on EC 3.1.3.43 - [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
3.1.3.43
-
RECOMMENDED NAME
GeneOntology No.
[pyruvate dehydrogenase (acetyl-transferring)]-phosphatase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
[pyruvate dehydrogenase (acetyl-transferring)] phosphate + H2O = [pyruvate dehydrogenase (acetyl-transferring)] + phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
additional information
SYSTEMATIC NAME
IUBMB Comments
[pyruvate dehydrogenase (acetyl-transferring)]-phosphate phosphohydrolase
A mitochondrial enzyme associated with EC 1.2.4.1 pyruvate dehydrogenase (acetyl-transferring), in the pyruvate dehydrogenase complex.
CAS REGISTRY NUMBER
COMMENTARY hide
9073-70-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
pea
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
strain BY4741
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
the enzyme is involved in the regulation of pyruvate dehydrogenase performing its activating dephosphorylation, together with phosphorylation and inactivation by pyruvate dehydrogenase kinase, PDK. Pyruvate dehydrogenase phosphatase PDP1 activity and expression is positively correlated with citrate synthase activity, regulation, overview
physiological function
-
allosteric activation of pyruvate dehydrogenase phosphatase and protein phosphatase 2Calpha leads to insulin-mimetic and insulin-sensitizing effects
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
-
-
-
?
peptide T-1
?
show the reaction diagram
-
phosphopeptide produced by tryptic digestion of phosphorylated pyruvate dehydrogenase
-
-
?
peptide T-2
?
show the reaction diagram
-
-
-
-
?
peptide T-3
?
show the reaction diagram
-
-
-
-
?
RRAS(P)VA
?
show the reaction diagram
-
-
-
-
?
[Asp8]tetradecapeptide + H2O
?
show the reaction diagram
-
-
-
-
?
[mothers against decapentaplegic]-phosphate + H2O
[mothers against decapentaplegic] + phosphate
show the reaction diagram
-
PDP1 directly dephosphorylates mothers against decapentaplegic (MAD) and inhibits signal transduction of decapentaplegic (DPP)
-
-
?
[pyruvate dehydrogenase (acetyl-transferring)] phosphate + H2O
[pyruvate dehydrogenase (acetyl-transferring)] + phosphate
show the reaction diagram
[pyruvate dehydrogenase (lipoamide)]-phosphate + H2O
?
show the reaction diagram
[pyruvate dehydrogenase (lipoamide)]-phosphate + H2O
[pyruvate dehydrogenase (lipoamide)] + phosphate
show the reaction diagram
additional information
?
-
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
[pyruvate dehydrogenase (acetyl-transferring)] phosphate + H2O
[pyruvate dehydrogenase (acetyl-transferring)] + phosphate
show the reaction diagram
-
-
-
-
?
[pyruvate dehydrogenase (lipoamide)]-phosphate + H2O
?
show the reaction diagram
[pyruvate dehydrogenase (lipoamide)]-phosphate + H2O
[pyruvate dehydrogenase (lipoamide)] + phosphate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
FAD
-
noncovalently bound to PDP1r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
Km: 1.4 mM
Zn2+
about 70% stimulation of activity in the presence of 0.01 mM Zn2+; about 70% stimulation of activity in the presence of 0.01 mM Zn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-dehydrolipoic acid
-
30% inhibition at 5 mM on phosphorylation at site 1 of E1, 20% inhibition at 5 mM on phosphorylation at site 2 of E1, 25% inhibition at 5 mM on phosphorylation at site 3 of E1
(R)-lipoic acid
-
30% inhibition at 5 mM on phosphorylation at site 1 of E1, 20% inhibition at 5 mM on phosphorylation at site 2 of E1, 25% inhibition at 5 mM on phosphorylation at site 3 of E1
(S)-lipoic acid
-
30% inhibition at 5 mM on phosphorylation at site 1 of E1, 20% inhibition at 5 mM on phosphorylation at site 2 of E1, 25% inhibition at 5 mM on phosphorylation at site 3 of E1
arsenite
-
together with NADH
Ca2+
-
antagonizes activation by Mg2+
Calmodulin
-
-
chlorpromazine
-
-
Dihydrolipoamide
-
-
fluphenazine
-
-
glyoxylate
-
at concentrations greater than 0.05 mM
myo-inositol cyclic 1,2-inositol phosphate phosphoglycan
-
from human plasma, antagonist of insulin, inhibits Mg2+ and spermine stimulation
-
N-ethylmaleimide
-
slight inhibition
NaCl
-
inhibits reactivation
p-nitrophenylphosphate
-
-
phosphate
ruthenium red
-
-
thioridazine
-
-
triflupromazine
-
-
Zn2+
about 20% decrease of activity in the presence of 0.01 mM Zn2+; about 20% decrease of activity in the presence of 0.01 mM Zn2+
additional information
obesity results in a 46% decrease in PDP activity while PDP isoform content is unchanged, 8 weeks of endurance training lead to a significant 1.4-2.2fold increase in isoform PDP1 activity of all muscle examined from obese rats; obesity results in a 46% decrease in PDP activity while PDP isoform content is unchanged, isoform PDP2 protein content is not affected by obesity or training
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1S)-1,5-anhydro-1-{[(1R,2R,3R,4S,5S,6S)-2,3,4,5-tetrahydroxy-6-methoxycyclohexyl]methyl}-D-galactitol
-
i.e. C-INS-2-OH the deaminated analogue of C-INS-2
(1S)-2-amino-1,5-anhydro-2-deoxy-1-{[(1R,2R,3R,4S,5S,6S)-2,3,4,5-tetrahydroxy-6-methoxycyclohexyl]methyl}-D-galactitol
-
i.e. C-INS-2, the C-glycoside of INS-2
2-tetradecylglycidate
-
together with insulin
4-O-beta-D-galactosaminyl-3-O-methyl-D-chiro-inositol
-
i.e. INS-2, allosteric activation, docking study using crystal structure of the enzyme PDHP1, PDB ID 2PNQ, and mechanism, overview
cysteine
-
reverses glyoxylate inhibition
Dichloroacetate
-
together with insulin
EGTA
-
-
inner lipoyl domain of dihydrolipoyl acetyltransferase
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component of substrate complex, structural requirements for binding and activation
-
inositol phosphoglycan P-type
linear stimulation; linear stimulation
-
Insulin
malate
-
-
NAD+
-
reverses NADH inhibition
protamine
-
-
putrescine
spermidine
spermine
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
29.3 - 55.1
p-nitrophenyl phosphate
0.625
peptide T-1
-
phosphopeptide produced by tryptic digestion of phosphorylated pyruvate dehydrogenase
-
0.22
peptide T-2
-
-
-
0.106
peptide T-3
-
-
-
0.053
RRAS(P)VA
-
with PDPc, a member of the protein phosphatase 2C family
-
0.018
RRAT(P)VA
-
with PDPc, a member of the protein phosphatase 2C family
-
0.0029 - 0.058
[Pyruvate dehydrogenase (lipoamide)]-phosphate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000001
-
in white gastrocnemius muscles, wet tissue
0.0000015
-
in soleus muscles, wet tissue
0.000002
-
in red gastrocnemius muscles in food-deprived rats, wet tissue
0.0000025
-
in red gastrocnemius muscles, wet tissue
0.0044
-
in soleus muscles, in food-deprived rats, extracted mitochondrial protein
0.005
-
in soleus muscles, extracted mitochondrial protein
0.0051
-
in white gastrocnemius, in food-deprived rats, extracted mitochondrial protein
0.0057
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in red gastrocnemius, in food-deprived rats, extracted mitochondrial protein
0.0058
-
in white gastrocnemius, extracted mitochondrial protein
0.0066
-
in red gastrocnemius, extracted mitochondrial protein
2.3
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
high expression
Manually annotated by BRENDA team
-
high expression
Manually annotated by BRENDA team
-
PDP1 is downregulated in obese subjects
Manually annotated by BRENDA team
-
lower mRNA expression compared to non diabetic control animals; mRNA expression
Manually annotated by BRENDA team
-
patients with congenital lactic acidemia
Manually annotated by BRENDA team
-
high level of isoform PDP1
Manually annotated by BRENDA team
-
high expression
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52600
-
PDP1c
92000 - 95000
-
gel electrophoresis, SDS-PAGE
95660
-
calculated after cloning, PCR and sequencing
95800
-
matrix-assisted laser desorption-ionization mass spectrometry
96000
-
PDP1r
100000
140000
-
gel filtration
150000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
additional information
-
overview on interactions and binding of subunits
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
needle like
-
hanging-drop method; hanging-drop method
-
PDP1c, by using the sitting-drop, vapor-diffusion method
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2 - 4
-
40% loss of activity within 8 days, 80% within 19 days
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
rabbit serum stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C for 1 month
-
-35C, 4 weeks
-
-70C, 400 mM KCl for 2 months no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
400-1000fold
-
75% purity after Ni-affinity chromatography
-
assay method
-
immobilized metal ion affinity chromatography (Ni2+), gel filtration; immobilized metal ion affinity chromatography (Ni2+), gel filtration
-
partially
-
partially, over 1000fold
-
recombinant catalytic subunit, one-step affinity chromatographic method
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli BL21
-
expression in S2 cells as GFP-construct; GST-fusion protein, expression in S2 cell line
-
His-tag fusion protein, expression in Escherichia coli BL21(DE3)
-
His-tagged SUMO version expressed in Escherichia coli BL21; His-tagged version expressed in Escherichia coli BL21
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
an oncogene BRAFV600E-induced senescence is accompanied by induction of the pyruvate dehydrogenase phosphatase 2
-
controlled cortical impact (CCI) induces a significant increase in PDP1 mRNA expression in ipsilateral cerebral cortex at 4 h and 24 h post CCI that return to basal level 72 h post CCI. PDP1 mRNA level increases transiently in ipsilateral hippocampal dentate gyrus and CA1-3 subfields 4 h post CCI
-
PDP1 mRNA expression in thalamus and other subcortical regions decrease persistently post controlled cortical impact
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D93A
-
loss of phosphatase activity
E93X
-
the nonsense mutation in the PDP1 gene shows a complete absence of isoform PDP1 protein in mitochondria, PDP2 can compensate for loss of PDP1 protein in a null patient; the nonsense mutation in the PDP1 gene shows a complete absence of isoform PDP1 protein in mitochondria, PDP2 can compensate for loss of PDP1 protein in a null patient
Y94F
-
phosphorylation-deficient mutant. Expression of the mutant in H-1299 cells leads to decreased proliferation under hypoxia and increased oxidative phosphorylation
D445A
-
almost complete loss of activity
D54A
-
almost complete loss of activity
N49A
-
38% of activity of wild type
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
molecular biology