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Information on EC 1.2.4.1 - pyruvate dehydrogenase (acetyl-transferring) and Organism(s) Escherichia coli and UniProt Accession P0AFG8
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1.2.4.1 pyruvate dehydrogenase (acetyl-transferring)IUBMB Comments
Contains thiamine diphosphate. It is a component (in multiple copies) of the multienzyme pyruvate dehydrogenase complex, EC 1.2.1.104, in which it is bound to a core of molecules of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, which also binds multiple copies of EC 1.8.1.4, dihydrolipoyl dehydrogenase. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.12.
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Word Map
- 1.2.4.1
- acetyl-coa
- dichloroacetate
- cardiac
-
tricarboxylic
-
lipoylation
- glycogen
- tca
-
pituitary-dependent
- acidosis
- hyperadrenocorticism
- dihydrolipoamide
-
x-linked
- lipoamide
-
warburg
- stearothermophilus
-
lipoic
- acth
- cortisol
- lipoate
-
hyperpolarized
-
crustacean
- histoplasmosis
- leigh
-
pigment-dispersing
-
vastus
- hypercortisolism
-
ketogenic
- phosphocreatine
- transacetylase
-
maple
- histoplasma
- trilostane
- pyranose
-
anaplerosis
- capsulatum
-
hernia
-
alpha2beta2
- prephenate
- acetylcarnitine
-
antimitochondrial
-
interbody
- agriculture
- medicine
- biotechnology
- synthesis
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
pdh, pdha1, mitochondrial pyruvate dehydrogenase, e1alpha, pyruvate dehydrogenase multienzyme complex, pyruvate dehydrogenase e1, pdhc-e1, mtpdc, pdhc e1, pyruvate dehydrogenase e1 component, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dehydrogenase, pyruvate
-
-
-
-
MtPDC
-
-
-
-
PDH
-
-
-
-
pyruvate decarboxylase
-
-
-
-
pyruvate dehydrogenase
-
-
-
-
pyruvate dehydrogenase complex
-
-
-
-
pyruvic acid dehydrogenase
-
-
-
-
pyruvic dehydrogenase
-
-
-
-
VEG220
-
-
-
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Vegetative protein 220
-
-
-
-
additional information
-
E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
active site interactions, reaction mechanism
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
reaction mechanism, role of water molecules
pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
reaction with phosphonolactylthiamine diphosphate gives a covalently bound, pre-decarboxylation reaction intermediate analogue tightly held in the active site through hydrogen bonds with H407, Y599, and H640
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-
SYSTEMATIC NAME
IUBMB Comments
pyruvate:[dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine 2-oxidoreductase (decarboxylating, acceptor-acetylating)
Contains thiamine diphosphate. It is a component (in multiple copies) of the multienzyme pyruvate dehydrogenase complex, EC 1.2.1.104, in which it is bound to a core of molecules of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, which also binds multiple copies of EC 1.8.1.4, dihydrolipoyl dehydrogenase. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.12.
CAS REGISTRY NUMBER
COMMENTARY
9014-20-4
-
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
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
-
-
-
?
alpha-ketobutyrate + Fe(CN)63- + H2O
hydroxyacetate + CO2 + Fe(CN)64-
-
-
-
?
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
pyruvate + [dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine
[dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
-
-
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
enzyme E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc, and catalyzes the first step of the multistep process
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
reaction of the citric acid or Krebs cycle
-
-
?
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
pyruvate + CoA + oxidized 2,6-dichlorophenolindophenol
acetyl-CoA + CO2 + reduced 2,6-dichlorophenolindophenol
-
artificial electron acceptor
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
additional information
?
-
reactions performed by the whole enzyme complex, overview
-
-
?
additional information
?
-
-
reactions performed by the whole enzyme complex, overview
-
-
?
additional information
?
-
-
overall reaction of the multienzyme complex, overview
-
-
?
additional information
?
-
-
N-terminal residues 1-45 of the pyruvate dehydrogenase complex E1 subunit interact with the E2 subunit and are required for activity of the complex but not for reductive acetylation of the E2 subunit
-
-
?
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
pyruvate + [dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine
[dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2
-
-
-
-
?
additional information
?
-
-
overall reaction of the multienzyme complex, overview
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
enzyme E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc, and catalyzes the first step of the multistep process
-
-
?
pyruvate + CoA + NAD+
acetyl-CoA + CO2 + NADH
reaction of the citric acid or Krebs cycle
-
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
in overall reaction of pyruvate dehydrogenase complex, pyruvate can be replaced by 2-ketobutyrate
-
?
pyruvate + lipoamide
S-acetyldihydrolipoamide + CO2
-
additional reactions of complex, e. g. reduction of K3Fe(CN)6
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
thiamine diphosphate
dependent on, 2 bound in the V-conformation in clefts between the 2 subunits, completely buried in the structure, binding structure
thiamine diphosphate
dependent on, binding structure and determinants, V conformation, K392 is important
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2-chlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
(3,4-dichlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
(3-chlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
(4-chlorophenyl)(dimethoxyphosphoryl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
(dimethoxyphosphoryl)(4-methylphenyl)methyl [3-(trifluoromethyl)phenoxy]acetate
-
(dimethoxyphosphoryl)(phenyl)methyl (2-chloro-5-methylphenoxy)acetate
-
(dimethoxyphosphoryl)(phenyl)methyl (4-chloro-2-methylphenoxy)acetate
-
(dimethoxyphosphoryl)(phenyl)methyl (4-chloro-3-methylphenoxy)acetate
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (2,3-dichlorophenoxy)acetate
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (2-chloro-5-methylphenoxy)acetate
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (3-fluorophenoxy)acetate
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2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-chloro-2-methylphenoxy)acetate
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2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-chloro-3-methylphenoxy)acetate
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2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-chlorophenoxy)acetate
-
2,2,2-trichloro-1-(dimethoxyphosphoryl)ethyl (4-fluorophenoxy)acetate
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5-((4-((4-chlorophenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
formation of intermolecular hydrogen bonding and halogen bonding. The 5-iodo-1,2,3-triazole and benzene ring play important roles in the biological activities of the compound. The iodine atom may participate in the halogen bonding with the negatively charged and can form a halogen bonding with the O atom of Asp521 in the active site of PDH-E1
O,O-dimethyl (2,3-dichlorophenoxyacetoxy)(furan-2-yl)-methylphosphonate
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O,O-dimethyl (2,3-dichlorophenoxyacetoxy)(thien-2-yl)-methylphosphonate
-
O,O-dimethyl (2,4-dichlorophenoxyacetoxy)(furan-2-yl)-methylphosphonate
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O,O-dimethyl (2,4-dichlorophenoxyacetoxy)(thien-2-yl)-methylphosphonate
-
O,O-dimethyl (2,6-dichlorophenoxyacetoxy)(furan-2-yl)-methylphosphonate
-
O,O-dimethyl (2,6-dichlorophenoxyacetoxy)(thien-2-yl)-methylphosphonate
-
O,O-dimethyl (2-chloro-5-methylphenoxyacetoxy)(furan-2-yl)methylphosphonate
-
O,O-dimethyl (2-chloro-5-methylphenoxyacetoxy)(thien-2-yl)methylphosphonate
-
O,O-dimethyl (4-chloro-2-methylphenoxyacetoxy)(furan-2-yl)methylphosphonate
-
O,O-dimethyl (4-chloro-2-methylphenoxyacetoxy)(thien-2-yl)methylphosphonate
-
O,O-dimethyl (4-chloro-3-methylphenoxyacetoxy)(furan-2-yl)methylphosphonate
-
O,O-dimethyl (4-chloro-3-methylphenoxyacetoxy)(thien-2-yl)methylphosphonate
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](2,4-dichlorophenyl)methyl]phosphonate
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](3-nitrophenyl)methyl]phosphonate
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](4-fluorophenyl)methyl]phosphonate
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sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](4-methoxyphenyl)methyl]phosphonate
-
sodium methyl [[[(2,4-dichlorophenoxy)acetyl]oxy](phenyl)methyl]phosphonate
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sodium o-methyl (2,4-dichlorophenoxyacetoxy)(2-chlorophenyl)methylphosphonate
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(3,4-dichlorophenyl)methyl phosphonate
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(4-chlorophenyl)methylphosphonate
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(4-methylphenyl)methylphosphonate
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(furan-2-yl)methylphosphonate
-
sodium o-methyl (2,4-dichlorophenoxyacetoxy)(pyridin-2-yl)methylphosphonate
-
thiamine 2-thiazolone diphosphate
crystallization data of complex with enzyme
thiamine thiazolone diphosphate
inhibits potently the E1 component of the pyruvate dehydrogenase multienzyme complex PDHc, competitive to cofactor thiamine diphosphate, binding structure and determinants, binding induced reorganisation of the active site conformation, mechanism, K392 is important, overview
4-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-iodo-1H-1,2,3-triazol-4-yl)methoxy)benzonitrile
-
exhibits very good enzyme-selective inhibition of PDH-E1 between pig heart and Escherichia coli and activity against Rhizoctonia solani and Botrytis cinerea even at 12.5 lg/ml
5-((4-((4-bromophenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
-
exhibits activity against Rhizoctonia solani and Botrytis cinerea even at 12.5 lg/ml
5-((4-((4-chloro-3-methylphenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
-
-
5-((4-((4-chlorophenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
-
exhibits activity against Rhizoctonia solani even at 12.5 lg/ml and almost 5.5 times more inhibitory potency against Botryttis cinerea than pyrimethanil
Fluoropyruvate
-
competitive with respect to pyruvate, both free and complex bound enzyme behave in the same manner
NaBH4
-
rapid inactivation in the presence of thiamine diphosphate, may reduce thiamine diphosphate to produce a reversible inhibitor
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
sigmoidal dependence on the concentration of pyruvate, Hill-coefficient: 1.85
-
0.1304
pyruvate
mutant enzyme Q408A, with 2,6-dichlorophenolindophenol, at 30°C
0.1714
pyruvate
mutant enzyme K410A, with 2,6-dichlorophenolindophenol, at 30°C
0.2012
pyruvate
mutant enzyme K411E, with 2,6-dichlorophenolindophenol, at 30°C
0.2336
pyruvate
mutant enzyme K411A, with 2,6-dichlorophenolindophenol, at 30°C
0.2609
pyruvate
wild type enzyme, with 2,6-dichlorophenolindophenol, at 30°C
0.6286
pyruvate
mutant enzyme E401A, with 2,6-dichlorophenolindophenol, at 30°C
0.7008
pyruvate
mutant enzyme K403A, with 2,6-dichlorophenolindophenol, at 30°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.081
pyruvate
mutant enzyme H407A, with 2,6-dichlorophenolindophenol, at 30°C
0.21
pyruvate
mutant enzyme K403E, with 2,6-dichlorophenolindophenol, at 30°C
0.39
pyruvate
mutant enzyme E401K, with 2,6-dichlorophenolindophenol, at 30°C
1.53
pyruvate
mutant enzyme K410E, with 2,6-dichlorophenolindophenol, at 30°C
3.07
pyruvate
mutant enzyme N404A, with 2,6-dichlorophenolindophenol, at 30°C
3.64
pyruvate
mutant enzyme E401A, with 2,6-dichlorophenolindophenol, at 30°C
4.41
pyruvate
mutant enzyme K403A, with 2,6-dichlorophenolindophenol, at 30°C
7.68
pyruvate
mutant enzyme K410A, with 2,6-dichlorophenolindophenol, at 30°C
19.03
pyruvate
mutant enzyme Q408A, with 2,6-dichlorophenolindophenol, at 30°C
25.12
pyruvate
mutant enzyme K411E, with 2,6-dichlorophenolindophenol, at 30°C
35.13
pyruvate
mutant enzyme K411A, with 2,6-dichlorophenolindophenol, at 30°C
37.9
pyruvate
wild type enzyme, with 2,6-dichlorophenolindophenol, at 30°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0101
4-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-iodo-1H-1,2,3-triazol-4-yl)methoxy)benzonitrile
Escherichia coli
-
isolated E1 component, pH 6.5, 37°C
0.0042
5-((4-((4-bromophenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
Escherichia coli
-
isolated E1 component, pH 6.5, 37°C
0.0051
5-((4-((4-chloro-3-methylphenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
Escherichia coli
-
isolated E1 component, pH 6.5, 37°C
0.0118
5-((4-((4-chlorophenoxy)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)methyl)-2-methylpyrimidin-4-amine
Escherichia coli
-
isolated E1 component, pH 6.5, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0048
-
Y177A mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate 2alpha-hydroxyethyl-thiamin diphosphate
0.00671
-
Y177F mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate 2alpha-hydroxyethyl-thiamin diphosphate
0.0098
-
wild-type enzyme, 2,6-dichlorophenolindophenol assay, substrate 2alpha-hydroxyethyl-thiamin diphosphate
0.087
-
Y177A mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate pyruvate
0.216
-
Y177F mutant enzyme, 2,6-dichlorophenolindophenol assay, substrate pyruvate
0.385
-
purified recombinant wild-type E1, with 2,6-dichlorophenolindophenol as electron acceptor
0.445
-
wild-type enzyme, 2,6-dichlorophenolindophenol assay, substrate pyruvate
1791
-
activity after reassociation of the purified enzyme with EC 2.3.1.12 and EC 1.8.1.4
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
enzyme E1 is a component of the pyruvate dehydrogenase multienzyme complex PDHc
Uniprot
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
99474
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
pyruvate dehydrogenase multienzyme complex component E1, 3 domains with alpha/beta fold, active sites are located at the interface between subunits, crystal structure
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with phosphonolactylthiamine diphosphate as structural and electrostatic analogue of alpha-lactylthiamin diphosphate. Presence of phosphonolactylthiamin diphosphate causes large conformational changes
preparation of catalytic subunit E1 of pyruvate dehydrogenase complex, without cofactors thiamine diphosphate and Mg2+, no evidence of disorder/order loop transformations. Comparison with holo-E1 enzyme and in an inhibitor complex with thiamine 2-thiazolone diphosphate
purified enzyme E1 in complex with inhibitor thiamine thiazolone diphosphate and Mg2+, sitting drop vapour diffusion method, reservoir solution: 15-20% PEG 2000 monomethyl ether, 5-10% 2-propanol, 0.2% NaN3, 100 mM HEPES, pH 7.00, 22°C, 4 weeks, X-ray diffraction structure determination and analysis at 2.09 A resolution, comparison with structure determined with bound cofactor thiamine diphosphate
purified recombinant pyruvate dehydrogenase multienzyme complex component E1, sitting drop vapor diffusion method, mixing of equal amounts of protein and precipitant solution of 0.006-0.01 ml, the latter containing 15-20% PEG2000 monomethyl ether, 10% propanol, 0.2% NaN3, and 60 mM HEPES, pH 7.1, 22°C, 2-5 weeks, native and selenomethionine crystals, X-ray diffraction structure determination and analysis at 1.85 A resolution
sitting drop vapour diffusion method with 15-20% PEG2000 monomethyl ether, 10% propanol, 0.2% NaN3 in 60 mM HEPES buffer (pH 7.05)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E401A
9.56% of overall wild type activity and 23.4% of wild type activity with 2,6-dichloroindolphenol
E401K
1.04% of overall wild type activity and 4.63% of wild type activity with 2,6-dichloroindolphenol
H407A
K403A
11.6% of overall wild type activity and 98.0% of wild type activity with 2,6-dichloroindolphenol
K403E
0.56% of overall wild type activity and 5.46% of wild type activity with 2,6-dichloroindolphenol
K410A
23.0% of overall wild type activity and 31.6% of wild type activity with 2,6-dichloroindolphenol
K410E
3.7% of overall wild type activity and 26.1% of wild type activity with 2,6-dichloroindolphenol
K411A
68.2% of overall wild type activity and 77.5% of wild type activity with 2,6-dichloroindolphenol
K411E
38.0% of overall wild type activity and 88.0% of wild type activity with 2,6-dichloroindolphenol
N404A
1.81% of overall wild type activity and 45.1% of wild type activity with 2,6-dichloroindolphenol
Q408A
31.5% of overall wild type activity and 112.1% of wild type activity with 2,6-dichloroindolphenol
D15A
-
site-directed mutagenesis, 0.19% remaining activity with NAD+ and 16% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
D549A
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
D7A
-
site-directed mutagenesis, 0.14% remaining activity with NAD+ and 63% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
D9A
-
site-directed mutagenesis, inactive with NAD+, 80% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
E12D
-
site-directed mutagenesis, 2.3% remaining activity with NAD+ and 90% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
E12Q
-
site-directed mutagenesis, 3.3% remaining activity with NAD+ and 59% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
E401K
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
E410K
-
CC-bond formation is dramatically slowed down (10-fold compared with E1ec) in E401K, the loop dynamics apparently greatly influences covalent addition of substrate to the enzyme-bound thiamine diphosphate
H407A
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
I11A
-
site-directed mutagenesis, 94% remaining activity with NAD+ and E1 activity with 2,6-dichlorophenolindophenol as electron acceptor is like the wild-type E1 activity
P10A
-
site-directed mutagenesis, unaltered activity with NAD+ and 50% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
R14A
-
site-directed mutagenesis, 0.25% remaining activity with NAD+ as electron acceptor, E1 activity with 2,6-dichlorophenolindophenol is like the wild-type E1 activity
T13A
-
site-directed mutagenesis, 13% remaining activity with NAD+ and 26% reduced E1 activity with 2,6-dichlorophenolindophenol as electron acceptor compared to the wild-type E1
Y177A
additional information
-
construction of several N-terminal E1 deletion mutants by tryptic or chymotryptic digest all showing reduced enzyme activity
H407A
crystallization data. Interaction between H407 and phosphonolactylthiamine diphosphate is essential for stabilization of two loop regions in the active site
H407A
0.15% of overall wild type activity and 12.0% of wild type activity with 2,6-dichloroindolphenol
Y177A
-
in the mutant, binding and reductive acetylation of E2p lipoyl domains are highly impaired
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50 mM phosphate buffer, pH 7.0, several months, no loss of activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
production of pyruvate in an Escherichia coli strain with central metabolic pathways modified. Genes ldhA, pflB, pta-ackA, poxB, ppc, frdBC are knocked out sequentially and full pyruvate dehydrogenase is retained. In batch fermentation with M9 medium, pyruvate yield and production rate reach 0.63 g/g glucose and 1.89 g/(1 h), respectively. The production of acetate, succinate, and other carboxylates is effectively controlled, while the pathways of convertion of pyruvate to phosphoenol pyruvate and acetyl CoA are enhanced
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Apfel, M.A.; Ikeda, B.H.; Speckhard, D.C.; Frey, P.A.
Escherichia coli pyruvate dehydrogenase complex. Thiamin pyrophosphate-dependent inactivation by 3-bromopyruvate
J. Biol. Chem.
259
2905-2909
1984
Escherichia coli
Lowe, P.N.; Leeper, F.J.; Perham, R.N.
Stereoisomers of tetrahydrothiamin pyrophosphate, potent inhibitors of the pyruvate dehydrogenase multienzyme complex from Escherichia coli
Biochemistry
22
150-157
1983
Escherichia coli
Saumweber, H.; Binder, R.; Bisswanger, H.
Pyruvate dehydrogenase component of the pyruvate dehydrogenase complex from Escherichia coli K12. Purification and characterization
Eur. J. Biochem.
114
407-411
1981
Escherichia coli
Reed, L.J.; Willms, C.R.
Purification and resolution of the pyruvate dehydrogenase complex (Escherichia coli)
Methods Enzymol.
9
247-265
1966
Escherichia coli
-
Nemeria, N.; Yan, Y.; Zhang, Z.; Brown, A.M.; Arjunan, P.; Furey, W.; Guest, J.R.; Jordan, F.
Inhibition of the Escherichia coli pyruvate dehydrogenase complex E1 subunit and its tyrosine 177 variants by thiamin 2-thiazolone and thiamin 2-thiothiazolone diphosphates. Evidence for reversible tight-binding inhibition
J. Biol. Chem.
276
45969-45978
2001
Escherichia coli, Homo sapiens
Arjunan, P.; Nemeria, N.; Brunskill, A.; Chandrasekhar, K.; Sax, M.; Yan, Y.; Jordan, F.; Guest, J.R.; Furey, W.
Structure of the pyruvate dehydrogenase multienzyme complex E1 component from Escherichia coli at 1.85 A resolution
Biochemistry
41
5213-5221
2002
Escherichia coli (P0AFG8), Escherichia coli
Park, Y.H.; Wei, W.; Zhou, L.; Nemeria, N.; Jordan, F.
Amino-terminal residues 1-45 of the Escherichia coli pyruvate dehydrogenase complex E1 subunit interact with the E2 subunit and are required for activity of the complex but not for reductive acetylation of the E2 subunit
Biochemistry
43
14037-14046
2004
Escherichia coli
Arjunan, P.; Chandrasekhar, K.; Sax, M.; Brunskill, A.; Nemeria, N.; Jordan, F.; Furey, W.
Structural determinants of enzyme binding affinity: the E1 component of pyruvate dehydrogenase from Escherichia coli in complex with the inhibitor thiamin thiazolone diphosphate
Biochemistry
43
2405-2411
2004
Escherichia coli (P0AFG8), Escherichia coli
Chandrasekhar, K.; Arjunan, P.; Sax, M.; Nemeria, N.; Jordan, F.; Furey, W.
Active-site changes in the pyruvate dehydrogenase multienzyme complex E1 apoenzyme component from Escherichia coli observed at 2.32 A resolution
Acta crystallogr. Sect. D
62
1382-1386
2006
Escherichia coli (P0AFG8), Escherichia coli
Arjunan, P.; Sax, M.; Brunskill, A.; Chandrasekhar, K.; Nemeria, N.; Zhang, S.; Jordan, F.; Furey, W.
A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct
J. Biol. Chem.
281
15296-15303
2006
Escherichia coli (P0AFG8), Escherichia coli
Xiong, Y.; Li, Y.; He, H.; Zhan, C.G.
Theoretical calculation of the binding free energies for pyruvate dehydrogenase E1 binding with ligands
Bioorg. Med. Chem. Lett.
17
5186-5190
2007
Escherichia coli
Peng, H.; Wang, T.; Xie, P.; Chen, T.; He, H.W.; Wan, J.
Molecular docking and three-dimensional quantitative structure-activity relationship studies on the binding modes of herbicidal 1-(substituted phenoxyacetoxy)alkylphosphonates to the E1 component of pyruvate dehydrogenase
J. Agric. Food Chem.
55
1871-1880
2007
Escherichia coli (P0AFG8)
Kale, S.; Arjunan, P.; Furey, W.; Jordan, F.
A dynamic loop at the active center of the Escherichia coli pyruvate dehydrogenase complex E1 component modulates substrate utilization and chemical communication with the E2 component
J. Biol. Chem.
282
28106-28116
2007
Escherichia coli (P0AFG8), Escherichia coli
Kale, S.; Ulas, G.; Song, J.; Brudvig, G.W.; Furey, W.; Jordan, F.
Efficient coupling of catalysis and dynamics in the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex
Proc. Natl. Acad. Sci. USA
105
1158-1163
2008
Escherichia coli
Balakrishnan, A.; Nemeria, N.S.; Chakraborty, S.; Kakalis, L.; Jordan, F.
Determination of pre-steady-state rate constants on the Escherichia coli pyruvate dehydrogenase complex reveals that loop movement controls the rate-limiting step
J. Am. Chem. Soc.
134
18644-18655
2012
Escherichia coli
Chandrasekhar, K.; Wang, J.; Arjunan, P.; Sax, M.; Park, Y.H.; Nemeria, N.S.; Kumaran, S.; Song, J.; Jordan, F.; Furey, W.
Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches
J. Biol. Chem.
288
15402-15417
2013
Escherichia coli
He, J.B.; He, H.F.; Zhao, L.L.; Zhang, L.; You, G.Y.; Feng, L.L.; Wan, J.; He, H.W.
Synthesis and antifungal activity of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives as pyruvate dehydrogenase complex E1 inhibitors
Bioorg. Med. Chem.
23
1395-1401
2015
Escherichia coli
He, J.; He, H.; Cai, M.; Zhao, F.; He, H.
Insight into the halogen bonding between PA-1 ligand and pyruvate dehydrogenase complex E1 component by crystal structure, DFT calculation, and molecular docking
J. Mol. Struct.
1199
126991
2020
Escherichia coli (P0AFG8)
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