Information on EC 2.7.11.4 - [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY hide
2.7.11.4
-
RECOMMENDED NAME
GeneOntology No.
[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP:[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphotransferase
The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the branched-chain 2-oxoacid dehydrogenase complex. Phosphorylation inactivates EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring).
CAS REGISTRY NUMBER
COMMENTARY hide
82391-38-6
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
mouse, C57BL/6J
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-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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the enzyme is involved in the regulation of the branched-chain alpha-keto acid dehydrogenase complex by inactivating it through phopshorylation, complex regulation and effects of the drug benzofibrate, overview
physiological function
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branched-chain alpha-keto acid dehydrogenase kinase is responsible for the regulation of branched-chain alpha-keto acid dehydrogenase complex, which is the rate-limiting enzyme in the catabolism of branched-chain amino acids
additional information
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activity of BDK practically corresponds with plasma insulin concentrations
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
ATP + histone II-S
?
show the reaction diagram
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
additional information
?
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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
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
-
activation
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Rb+
-
activation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(N-Morpholino)propane sulfonate buffer
2-Chloroisohexanoate
2-oxo-3-methylpentanoate
2-oxobutanoate
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2-oxohexanedioate
2-Oxohexanoate
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2-oxoisocaproate
2-oxoisopentanoate
2-Oxopentanoate
3-methyl-2-oxobutanoate
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4-(2-Thienyl)-2-oxo-3-butenoate
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2 mM
4-(3-Thienyl)-2-oxo-3-butenoate
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2 mM
4-hydroxyphenylacetate
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4-hydroxyphenyllactate
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weak
4-hydroxyphenylpyruvate
4-methyl-2-oxopentanoate
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acetate
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weak, in vivo and in vitro
acetoacetyl-CoA
alpha-Chloroisocaproate
alpha-Ketoisocaproate
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inhibits the enzyme by releasing it from the BCKD complex via dissociation
alpha-ketoisovalerate
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inhibits the enzyme by releasing it from the BCKD complex via dissociation
branched-chain 2-oxo acids
CDP
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50% inhibition at 0.4 mM, inhibition can be reversed by 2 mM Mg2+
Clofibric acid
CTP
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50% inhibition at 0.25 mM, inhibition can be reversed by 2 mM Mg2+
dexamethasone
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decreases enzyme expression level in renal tubule cells
Dichloroacetate
diphosphate
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Furfurylidenepyruvate
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1.85 mM
GDP
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50% inhibition at 0.2 mM, inhibition can be reversed by 2 mM Mg2+
GTP
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50% inhibition at 0.06 mM, inhibition can be reversed by 2 mM Mg2+
heparin
isobutyryl-CoA
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isovaleryl-CoA
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methylmalonyl-CoA
Mg2+
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at concentrations above 1.5 mM, activation below
MgATP2-
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n-Octanoate
phenylacetate
Phenyllactate
phenylpyruvate
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in vivo and in vitro
pyruvate
thiamine
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thiamine diphosphate
UDP
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50% inhibition at 0.25 mM, inhibition can be reversed by 2 mM Mg2+
UTP
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50% inhibition at 0.1 mM, inhibition can be reversed by 2 mM Mg2+
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Histone H3
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1.5 to 3fold
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poly-L-arginine
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1.5 to 3fold
poly-L-lysine
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1.5 to 3fold
protamine
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1.5 to 3fold
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004 - 0.025
ATP
0.0126 - 0.013
MgATP2-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0542 - 0.475
phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.5
2-Chloroisohexanoate
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37C
0.00092
2-oxoisocaproate
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pH 7.5, 30C
0.00048 - 0.0089
4-methyl-2-oxopentanoate
0.00027 - 0.27
ADP
0.004
diphosphate
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pH 7.5, 30C
4.5
Furfurylidenepyruvate
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-
0.0059
thiamine
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pH 7.5, 30C
0.0032 - 0.0164
thiamine diphosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.006 - 0.031
alpha-Chloroisocaproate
0.0046 - 0.008
thiamine diphosphate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0247
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without added salt
0.0268
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liver enzyme
0.0357 - 0.09
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heart enzyme, depending on purification method
0.0357
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heart enzyme
0.05
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recombinant enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.3
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about half-maximal activity at pH 6.5 and 8.3
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.5
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native PAGE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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liver cell line
Manually annotated by BRENDA team
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undifferentiated myoblast cell line
Manually annotated by BRENDA team
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LLC-PK1 renal tubule cell line expressing the Rattus norvegicus glucocorticoid receptor GR
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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fibroblast cell line
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
43280
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calculated from amino acid sequence
44000 - 45000
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SDS-PAGE
460000
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gel filtration
2000000
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above 2000000, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
dimerizes through direct interaction of two opposing nucleotide-binding domains, crystallographic data
monomer
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1 * 43000, uncomplexed kinase, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
vapor diffusion method
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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loss of activity during purification at pH-values below 7
640575
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
precipitation of branched-chain oxo acid dehydrogenase enzyme complex at acid pH-values, especially below 6.5, results in specific loss of kinase activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
labile enzyme, best stored at -70C in the presence of DTT
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5000fold
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alpha-ketoacid dehydrogenase complex
copurifies with EC 1.2.4.4
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from liver and heart, homogeneity
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from purified branched-chain alpha-keto acid dehydrogenase complex
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liver enzyme, heart enzyme and recombinant enzyme expressed in Escherichia coli
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partially from mitochondria
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
BCKD kinase transcription regulation, overview
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BDK quantitative real-time PCR expression analysis
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BDK semi-quantitative real-time PCR expression analysis
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cloned and expressed in Escherichia coli
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DNA sequence determination and analysis, promotor region footprinting, expression analysis, mechanism of the enzyme expression regulation
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fragments of the enzyme cloned into firefly luciferase plasmid
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fusion protein with maltose-binding protein
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is reduced by 5% by bezafibrate
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insulin is known to increase the enzyme expression in cultured rat hepatocytes
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G671C
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naturally occuring mutation, on chromosome 16, leads to the substitution of a highly conserved arginine with a proline at position 224 in BCKDK
R224P
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naturally occuring mutation, leading to disruption of the beta sheet in a flexible linker domain, structure modeling
additional information
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identification of mutations from autism patients , e.g. in exon 4 (C466T) resulting in a premature stop codon at amino acid position 156, prior to the kinase domain, or a single base deletion (c.G222del) in exon 2 leading to frame-shift terminating the protein at position 74 of 412 amino acids, whole-exome sequencing from two consanguineous families
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution with lipoylated recombinant E2
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