Information on EC 2.7.11.2 - [pyruvate dehydrogenase (acetyl-transferring)] kinase

New: Word Map on EC 2.7.11.2
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
2.7.11.2
-
RECOMMENDED NAME
GeneOntology No.
[pyruvate dehydrogenase (acetyl-transferring)] kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
mechanism
-
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
mechanism
-
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
mechanism
-
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
molecular modeling of the catalytic domain, structure
Q63065
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
structure of the nucleotide binding pocket with responsible His115 residue and of the catalytic site
-
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
His121 is involved in the catalytic reaction
-
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)]phosphate
show the reaction diagram
allosteric R-T equilibrium as the mechanism for L2-stimulated PDK3 activity, the active cleft undergoes a conformational change from closed to open conformation upon stimulation by L2 binding releasing ADP
-
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)]phosphate
show the reaction diagram
ordered reaction mechanism with ATP binding before E1, ordered reaction mechanism with ATP binding first, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[pyruvate dehydrogenase (acetyl-transferring)] phosphotransferase
The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the pyruvate dehydrogenase complex in mammals. Phosphorylation inactivates EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring).
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
kinase (phosphorylating), pyruvate dehydrogenase
-
-
-
-
pyruvate dehydrogenase kinase
-
-
-
-
pyruvate dehydrogenase kinase (phosphorylating)
-
-
-
-
pyruvate dehydrogenase kinase activator protein
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9074-01-5
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
multi-copy gene BnPDK1
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
-
Manually annotated by BRENDA team
4 different isozymes: PDK1, PDK2, PDK3, PDK4; isozyme development via gene duplication, gene locations are: PDK1 in chromosome 2, PDK2 in chromosome 17, PDK3 in chromosome Xp22, PDK4 in chromosome 7q21q22
-
-
Manually annotated by BRENDA team
female and male, isozyme PDK1-PDK4
-
-
Manually annotated by BRENDA team
gene PDK1, isozyme PDK1
-
-
Manually annotated by BRENDA team
isoyzmes PDK-2 and PDK-4
-
-
Manually annotated by BRENDA team
isozyme 4, i.e. PDK4; isozyme PDK4
SwissProt
Manually annotated by BRENDA team
isozyme PDHK2
-
-
Manually annotated by BRENDA team
isozyme PDHK2; isozyme PDHK2
-
-
Manually annotated by BRENDA team
isozyme PDK2
-
-
Manually annotated by BRENDA team
isozyme PDK3
-
-
Manually annotated by BRENDA team
isozyme PDK4
-
-
Manually annotated by BRENDA team
isozymes PDHK1, PDHK2, PDHK3, and PDHK4
-
-
Manually annotated by BRENDA team
isozymes PDK1-4
-
-
Manually annotated by BRENDA team
isozymes PDK2 and PDK3
-
-
Manually annotated by BRENDA team
at least 4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
-
Manually annotated by BRENDA team
C75BL/6 mice
-
-
Manually annotated by BRENDA team
isozyme PDK4
-
-
Manually annotated by BRENDA team
male C75Bl mice
-
-
Manually annotated by BRENDA team
ob/ob mouse, animal model for diabetes
-
-
Manually annotated by BRENDA team
Mus musculus C75BL/6
C75BL/6 mice
-
-
Manually annotated by BRENDA team
var. Alaskan Marvel
-
-
Manually annotated by BRENDA team
3 isozymes PDHK1, PDHK2, PDHK4
-
-
Manually annotated by BRENDA team
3 isozymes PDHK1, PDHK2, PDHK4; female Wistar rats; selective increase in amount of PDHK4 protein in both hyperthyroidism and high-fat feeding
-
-
Manually annotated by BRENDA team
4 different isozymes: PDK1, PDK2, PDK3, PDK4
-
-
Manually annotated by BRENDA team
4.5fold higher specific activity in starved than in fed rats; two kinases: pyruvate dehydrogenase-intrinsic activity and free pyruvate dehydrogenase kinase
-
-
Manually annotated by BRENDA team
female Sprague-Dawley rats, young and middle-aged Otsuka Long-Evans Tokushima Fatty rats, isozymes PDK2 and PDK4
-
-
Manually annotated by BRENDA team
female Wistar rats; isozymes PDK2 and PDK4
-
-
Manually annotated by BRENDA team
from heart
SwissProt
Manually annotated by BRENDA team
gene Pdk1
-
-
Manually annotated by BRENDA team
isozyme PDK1
SwissProt
Manually annotated by BRENDA team
isozyme PDK2
-
-
Manually annotated by BRENDA team
isozyme PDK2
SwissProt
Manually annotated by BRENDA team
isozyme PDK2, Protein Data Bank: 1JM6
-
-
Manually annotated by BRENDA team
isozymes PDK1 and PDK2
-
-
Manually annotated by BRENDA team
isozymes PDK1, PDK2, and PDK4
-
-
Manually annotated by BRENDA team
isozymes PDK1, PDK2, PDK3, and PDK4
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
Wistar rats, isozymes PDHK1, PDHK2, PDHK3, and PDHK4
-
-
Manually annotated by BRENDA team
Rattus norvegicus Fawn-Hooded
-
-
-
Manually annotated by BRENDA team
mitochondrial precursor; isozyme PDK4
SwissProt
Manually annotated by BRENDA team
strain BY4741, gene YIL042c
-
-
Manually annotated by BRENDA team
strain BY4741, gene YIL042c
-
-
Manually annotated by BRENDA team
Yorkshire and Chinese indigenous breed Meishan pigs
UniProt
Manually annotated by BRENDA team
female frogs
-
-
Manually annotated by BRENDA team
at least 2 isozymes
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
enzyme inhibition results in increased pyruvate dehydrogenase complex activity. Oxidation of Cys45 or Cys392 inhibits PDHK2 activity. Dimer formation is not essential for PDHK2 inactivation via Cys392 oxidation, although it may potentiate it
malfunction
-
expression of phosphorylation-deficient, catalytic hypomorph PDHK1 mutants in cancer cells leads to decreased cell proliferation under hypoxia and increased oxidative phosphorylation with enhanced mitochondrial utilization of pyruvate, and reduced tumor growth in xenograft nude mice. Cells expressing catalytically less active mPDHK1 mutants, including Y134F and Y239/240F, rely more on oxidative phosphorylation for ATP production and cell proliferation compared to cells with mPDHK1 wild-type
malfunction
-
FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension, overview. The bioenergetic impairment and right ventricular dysfunction can be reversed by dichloroacetate
malfunction
-
knockdown of PDH kinase 1 does not affect basal insulin secretion but, remarkably, insulin secretion in response to 16.7 mM glucose increases more vigorously than in negative control cells. The metabolite profile of cells with PDH kinase 1 knockdown is significantly different from that of the control cells, expecially the tricarboxylic acid cycle intermediates malate, fumarate and 2-oxoglutarate, overview
malfunction
-
pyruvate dehydrogenase activity is 2.5fold higher at rest in PDK4 knockout mouse muscle compared to the wild-type, and about 2fold in activated muscle at low and high intensity contraction
malfunction
-
wild-type mouse primary cortical neurons treated with amyloid beta peptide or cortical tissue extracts from 12-month-old APPswe/PS1dE9 transgenic mice show decreased expression of lactate dehydrogenase A and PDK1 when compared with controls
malfunction
Rattus norvegicus Fawn-Hooded
-
FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension, overview. The bioenergetic impairment and right ventricular dysfunction can be reversed by dichloroacetate
-
metabolism
-
metabolic profiling and glucose-stimulated insulin secretion in pancreatic beta cells with and without knockdown of the enzyme, overview
metabolism
Q3LTL2
mitochondrial pyruvate dehydrogenase complex, a key multienzyme system catalyzing the irreversible conversion of pyruvate to acetyl-CoA and NADH with CO2 as a byproduct, is regulated through inactivation by pyruvate dehydrogenase kinase phosphorylation and reactivation by phospho-PDH phosphatase dephosphorylation
metabolism
-
p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2, which negatively regulates the pyruvate dehydrogenase complex. Decreased levels of Pdk2 and P-Pdc in turn promote conversion of pyruvate into acetyl-CoA instead of lactate
metabolism
-
PDHK2 is responsible for short-term metabolic responses
physiological function
Q64536
phosphorylation (activation) of pyruvate dehydrogenase
physiological function
C1IHT9
regulation and controlling of the pyruvate dehydrogenase complex activity in skeletal muscles by phosphorylation
physiological function
-
the mitochondrial pyruvate dehydrogenase complex, PDC, is down-regulated by phosphorylation catalyzed by pyruvate dehydrogenase kinase isoforms
physiological function
-
expression of PDK4 is regulated by its regulatory transcription factor, FOXO1. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
physiological function
-
PDK1 phosphorylates and inhibits pyruvate dehydrogenase, an enzyme responsible for the conversion of pyruvate to acetyl-CoA
physiological function
-
Pdk2 is seen as the key control point in conversion of pyruvate to acetyl-CoA reaction because it responds allosterically to rapid local changes in substrate and product: Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
physiological function
-
Pdk2 is seen as the key control point in conversion of pyruvate to acetyl-CoA reaction because it responds allosterically to rapid local changes in substrate and product: Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase. P53-dependent apoptosis requires downregulation of Pdk2, early apoptotic events do not occur unless p53 can downregulate the transcription of Pdk2
physiological function
-
pyruvate dehydrogenase kinase 4 is one of four PDH kinases regulating the function of the pyruvate dehydrogenase complex, PDH. PDK4 is responsible for reducing PDH activity during low- to moderate-intensity muscle stimulation for contraction of the extensor digitorum muscle
physiological function
Q3LTL2
pyruvate dehydrogenase kinase is a negative regulator of the mitochondrial pyruvate dehydrogenase complex, which plays a key role in intermediary metabolism
physiological function
-
regulation of Pdk4 gene expression by the CCAAT/enhancer-binding protein beta, i.e. C/EBPbeta, which modulates the expression of multiple hepatic genes including those involved in metabolism, development, and inflammation. C/EBPbeta induces Pdk4 gene expression and decreases pyruvate dehydrogenase complex activity, and it participates in the T3 induction of the Cpt1a and Pdk4 genes, overview
physiological function
-
tyrosine phosphorylation activates PDHK1 to promote the Warburg effect and tumor growth in cancer cells. Oncogenic FGFR1 is localized in mitochondria in cancer cells, where it phosphorylates PDHK1
physiological function
Rattus norvegicus Fawn-Hooded
-
expression of PDK4 is regulated by its regulatory transcription factor, FOXO1. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
-
metabolism
Q16654
the mitochondrial pyruvate dehydrogenase complex, PDC, activity is tightly regulated by four members of a family of pyruvate dehydrogenase kinase isoforms, PDK1-4, which phosphorylate and inactivate PDC
additional information
Q16654
ADP-bound PDK4 has a slightly wider active-site cleft and a more disordered ATP lid compared with AMPPNP-bound PDK4, binding structures of ADP and AMPPNP to isozyme PDK4, detailed overview. The width of the active-site cleft of PDK4 is determined by the location of the Tyr332 side chain
additional information
-
overexpression of lactate dehydrogenase A or PDK1 in the B12 central nervous system cell line confers resistance to amyloid beta, H2O2, and staurosporine. Increased survival in cells overexpressing lactate dehydrogenase A or PDK1, associated with decreased mitochondrial membrane potential
additional information
-
overexpression of lactate dehydrogenase A or PDK1 in the B12 central nervous system cell line confers resistance to amyloid beta, H2O2, and staurosporine. Increased survival in cells overexpressing lactate dehydrogenase A or PDK1. Increased survival in cells overexpressing LDHA or PDK1 is associated with decreased mitochondrial membrane potential
additional information
-
three-dimensional structures of the two isozymes PDK3 and PDK4 by homology modeling based on the crystal structures of mammalian PDKs, overview. Important structural differences modify the accessibility of the nucleotide binding site in the two isozymes, molecular dynamics and sequence/structure comparisons
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of serine residues of the E1 PDC component
-
-
ir
ATP + Ac-YHGHSMSDPGVSYR
ADP + [Ac-YHGHSMSDPGVSYR]phosphate
show the reaction diagram
-
recombinant enzyme, synthetic peptide substrate
-
-
?
ATP + casein
ADP + casein phosphate
show the reaction diagram
-
kidney enzyme, low activity
-
?
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
show the reaction diagram
-
the enzyme is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, which negatively regulates the complex by reversible phosphorylation of its Pda1p subunit, overview
-
-
?
ATP + PDHA1
ADP + phosphorylated PDHA1
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
a small pocket in the N-terminal region of PDHK2 is involved in enzyme regulation, the pocket is formed by residues L53, Y157, Y80, S83, I111, R112, H115, S153, R154, I157, R158, I161
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
enzyme has an important role in control of glucose homeostasis
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
PDHK plays a key role in controlling the balance between glucose and lipid oxidation according to substrate supply, PDHK inhibition leads to increased PDH activity increasing glucose oxidation
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
PDK is involved in fatty acid metabolism
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation by PDK inhibits the pyruvate dehydrogenase complex, PDK plays a regulatory role in glucose metabolism, PDK4 expression is regulated by hepatic nuclear factor 4 and peroxisome proliferator-activated receptor gamma coactivator, PGC-1alpha
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of E2-bound E1
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
pyruvate dehydrogenase kinase is a negative regulator in the mitochondrial pyruvate dehydrogenase complex and plays a pivotal role in controlling TCA cycle and cell respiration
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
PDH inactivation by phosphorylation at serine residues of the E1alpha component of the complex
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
PDK activity as component of the pyruvate dehydrogenase complex PDC binding the lipoyl domain of E2
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of 3 serine residues in the pyruvate dehydrogenase domain of the pyruvate dehydrogenase complex
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of 3 serine residues of the E2 domain, isozyme-specific activity
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of E2-bound E1, higher activity with reduced E2, enzyme stimulation reduces the amount of bound ADP
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of serine residues of the E1 component of pyruvate dehydrogenase complex PDC
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of serine residues of the E1 PDC component
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
the pyruvate dehydrogenase is a component of the pyruvate dehydrogenase complex, PDC
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
Q64536
Kd for ATP is 2.5 micromol, for ADP 10.6 micromol and for dichloroacetate 226 micromol
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
-
PDHK4 inhibits the pyruvate dehydrogenase complex by phosphorylation during starvation, regulation mechanism, overview
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
-
PDHK2 is an integral component of pyruvate dehydrogenase complex tightly bound to the inner lipoyl-bearing domains L2 of the dihydrolipoyl transacetylase component E2 of pyruvate dehydrogenase complex
-
-
?
ATP + YHGHSMSDPGVSYR
ADP + ?
show the reaction diagram
Q16654
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
C1IHT9
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
phosphorylation at Ser292 by PDK1, reversible phosphorylation of alpha2beta2-heterotetrameric pyruvate dehydrogenase complex, i.e. E1, phosphorylation at Ser292 within the active-site loop structure of E1alpha by PDK1. Substrate mutation of Asp295 to Ala, Asn, or Leu greatly reduces phosphorylation of Ser292, while mutation of Gly297 has relatively little effect. AtPDC E1alpha S298A mutant is phosphorylated by AtPDK. Activity of the enzyme with different substrate mutants, overview
-
-
r
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q16654
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
O02623
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
highly specific for the substrate
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
pyruvate dehydrogenase complex substrate is inactivated by ATP-dependent phosphorylation of 3 serine residues on the E1 subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
incorporates gamma-phosphate from ATP into E1-component of pyruvate dehydrogenase-complex alpha-subunit
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
the 3 serine phosphorylation sites of the E1 subunit are specifically and with different activity phosphorylated by the 4 isozymes, overview: site 1 is preferably utilized by PDK2, site 2 by PDK3, and site 3 is exclusively utilized by PDK1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
optimum activity within a small range of ionic strength of 0.03-0.05 M
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
recombinant hybrid enzyme of PDK1 and PDK2 phosphorylates site 3 with lower activity than the PDK1 homodimer, serine phosphorylation site 3 of subunit E1 is exclusively phosphorylated by isozyme PDK1, not by PDK2, which prefers site 1 over site 2
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
isozyme PDK2 can phosphorylate free pyruvate dehydrogenase complex but bound dihydrolipoyl transacetylase enhances the rate up to 5000fold
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q9SBJ1
substrate is kinase-depleted pyruvate dehydrogenase complex from Zea mays
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation sites are 3 Ser-residues in the alpha-subunit, i.e. E1, MW 41000, of pyruvate dehydrogenase
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation sites are 3 Ser-residues in the alpha-subunit, i.e. E1, MW 41000, of pyruvate dehydrogenase
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation sites are 3 Ser-residues in the alpha-subunit, i.e. E1, MW 41000, of pyruvate dehydrogenase
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q9SBJ1
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
beta-subunit harbors a regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
enzyme regulation in the heart depends on thyroid hormone and lipid status
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
enzyme regulates glucose oxidation by pyruvate dehydrogenase complex, isozyme PDHK1 is of more potential importance in adult heart than the other isozymes
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q16654
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
O02623
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
isozyme PDK3 has a putative regulatory role of the pyruvate dehydrogenase complex in sperm
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
involved in regulation of mitochondrial pyruvate dehydrogenase complex
-
ir
additional information
?
-
-
no activity with histones of calf thymus type II-A
-
-
-
additional information
?
-
-
little, if any activity with casein of bovine kidney, no activity with histones of calf thymus type II-A, VI-S and VIII-S
-
-
-
additional information
?
-
Q9SBJ1
performs pH-dependent autophosphorylation on serine residues
-
-
-
additional information
?
-
-
no autophosphorylation
-
-
-
additional information
?
-
O02623
no autophosphorylation
-
-
-
additional information
?
-
-
no autophosphorylation
-
-
-
additional information
?
-
-
activity depends on the buffer system, the reduction status of the lipoyl groups and on the serine phosphorylation site of the E1 subunit of the pyruvate dehydrogenase complex used as substrate
-
-
-
additional information
?
-
-
performs autophosphorylation
-
-
-
additional information
?
-
Q63065
binding of homodimers of PDK1 and PDK2, respectively and the heterodimer of PDK1+PDK2 to the pyruvate dehydrogenase complex via dihydrolipoyl transacetylase
-
-
-
additional information
?
-
-
no activity with glycogen synthase a and rabbit skeletal muscle phosphorylase b
-
-
-
additional information
?
-
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms
-
-
-
additional information
?
-
-
fibrates induction of PDK4 might be coupled to an decrease in serum triglycerides and fatty acid levels which can cause protein degradation in muscles, PDK4 induction is increased in acute rhabdomyolysis
-
-
-
additional information
?
-
-
PDK regulates the pyruvate dehydrogenase multienzyme complex activity
-
-
-
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, complex regulation and the molecular mechanisms
-
-
-
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, detailed overview and modeling of the complex regulation and the molecular mechanisms
-
-
-
additional information
?
-
-
peroxisome proliferator-activated receptors and insulin have regulatory functions in expression of isozymes PDK2 and PDK4, regulation mechanism
-
-
-
additional information
?
-
-
pyruvate dehydrogenase kinase is part of the pyruvate dehydrogenase complex, regulation and component interactions, PDK2 binds the inner lipoyl domain L2, preferably in dimeric form, overview
-
-
-
additional information
?
-
-
rapid upregulation of isozyme PDK4 in skeletal muscle after prolonged exercise, PDK activity is increased during prolonged exercise, physiologic/metabolic state, overview
-
-
-
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
-
additional information
?
-
-
the PDK/PDH pathway is reduced by 73% in non small cell lung carcinoma contributing to hypoxia-inducible factor-1 stability and aerobic glycolysis
-
-
-
additional information
?
-
-
a homodimer of pyruvate dehydrogenase kinase is an integral part of the pyruvate dehydrogenase complex, PDC, to which it is anchore primarily through the inner lipoyl-bearing domains L2 of transacetylase component, binding structure, catalytic cycle of PDHK and its translocation over the PDC surface is thought to be mediated by the symmetric and asymmetric modes, in which the PDHK dimer binds to two and one L2-domain(s), respectively, overview
-
-
-
additional information
?
-
-
hypoxia-inducible factor HIF-1, inducible e.g. by CoCl2, mediates the expression of PDK1, which inhibits the pyruvate dehydrogenase in the tricarboxylic cycle by phosphorylation, high PDK1 activity increases the ATP levels and prevents hypoxia-induced reactive oxygen species generation and apoptosis
-
-
-
additional information
?
-
-
PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes
-
-
-
additional information
?
-
-
PDHK2 is required for binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase of the pyruvate dehydrogenase complex
-
-
-
additional information
?
-
Q15118
PDK isozymes are molecular switches that downregulate the pyruvate dehydrogenase complex PDC by reversible phosphorylation in mitochondria, L2 domain binding structure of isozyme PDK3, overview
-
-
-
additional information
?
-
-
PDK4 expression is specifically regulated by retinoic acids, via retinoid receptors, and trichostatin A, an inhibitor of histone deacetylase
-
-
-
additional information
?
-
-
PDK4 is involved in metabolic changes after induction by high-fat/low carbohydrate diet, overview
-
-
-
additional information
?
-
-
phosphorylation of the pyruvate dehydrogenase complex PDC by the pyruvate dehydrogenase kinases PDK2 and PDK4 inhibits PDC activity, expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA, transcriptional regulation of the PDK4 gene by the estrogen-related receptors ERRalpha and ERRgamma, the ERRs are orphan nuclear receptors whose physiological roles include the induction of fatty acid oxidation in heart and muscle, overview
-
-
-
additional information
?
-
-
pyruvate dehydrogenase kinase isozymes are the molecular switch that down-regulates activity of the pyruvate dehydrogenase complex through reversible phosphorylation, interaction of PDK with L2 within the pyruvate dehydrogenase complex, overview
-
-
-
additional information
?
-
Q15118
ligand binding by isozyme PDK1 involves the conserved Ser75
-
-
-
additional information
?
-
-
modelling of the molecular mechanisms of recognition of the inner lipoyl-bearing domain of dihydrolipoyl transacetylase and of the blood glucose-lowering compound AZD7545 by pyruvate dehydrogenase kinase 2, residues L140, K173, I176, E179 are essential for recognition, and to a lesser extent also D164, D172, and A174, PDHK2 residues forming interfaces with L2, i.e. K17, P22, F31, F44, R372, and K391, are also critical for the maintenance of enhanced PDHK2 activity in the E2-bound state
-
-
-
additional information
?
-
-
PD kinase isozymes PDK1, PDK2, PDK3 and PDK4, reduce the active form of pyruvate dehydrogenase complex, PDC, via binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase E2, PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory domain, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overall reaction of the pyruvate dehydrogenase complex, overview
-
-
-
additional information
?
-
-
pyruvate dehydrogenase Asp295 plays an important role in stabilizing the active-site loop structure of the pyruvate dehydrogenase, facilitating transfer of the gamma-phosphate from ATP to the Ser residue at regulatory site one of E1alpha, substrate structure, overview
-
-
-
additional information
?
-
Mus musculus C75BL/6
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + Pda1p subunit
ADP + phosphorylated Pda1p subunit
show the reaction diagram
-
the enzyme is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, which negatively regulates the complex by reversible phosphorylation of its Pda1p subunit, overview
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
ir
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
a small pocket in the N-terminal region of PDHK2 is involved in enzyme regulation, the pocket is formed by residues L53, Y157, Y80, S83, I111, R112, H115, S153, R154, I157, R158, I161
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
enzyme has an important role in control of glucose homeostasis
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
PDHK plays a key role in controlling the balance between glucose and lipid oxidation according to substrate supply, PDHK inhibition leads to increased PDH activity increasing glucose oxidation
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
PDK is involved in fatty acid metabolism
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation by PDK inhibits the pyruvate dehydrogenase complex, PDK plays a regulatory role in glucose metabolism, PDK4 expression is regulated by hepatic nuclear factor 4 and peroxisome proliferator-activated receptor gamma coactivator, PGC-1alpha
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
phosphorylation of E2-bound E1
-
-
?
ATP + pyruvate dehydrogenase
ADP + phosphorylated pyruvate dehydrogenase
show the reaction diagram
-
pyruvate dehydrogenase kinase is a negative regulator in the mitochondrial pyruvate dehydrogenase complex and plays a pivotal role in controlling TCA cycle and cell respiration
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
-
-
-
-
?
ATP + pyruvate dehydrogenase complex
ADP + phosphorylated pyruvate dehydrogenase complex
show the reaction diagram
-
PDHK4 inhibits the pyruvate dehydrogenase complex by phosphorylation during starvation, regulation mechanism, overview
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
C1IHT9
-
-
-
?
ATP + [pyruvate dehydrogenase (acetyl-transferring)]
ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
phosphorylation at Ser292 by PDK1
-
-
r
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q16654
-
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q9SBJ1
the enzyme is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
beta-subunit harbors a regulatory role
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
enzyme regulation in the heart depends on thyroid hormone and lipid status
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tissue-specific regulation of the pyruvate dehydrogenase complex in order to adjust glucose consumption
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
enzyme regulates glucose oxidation by pyruvate dehydrogenase complex, isozyme PDHK1 is of more potential importance in adult heart than the other isozymes
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q16654
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Q63065
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
O02623
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
catalyzes inactivation through phosphorylation of pyruvate dehydrogenase complex EC 1.2.4.1
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
high-fat feeding increases the expression of isozyme PDK2, but not of PDK4, hyperthyroidism increases the expression of both isozymes, physiological implications
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
isozyme PDK3 has a putative regulatory role of the pyruvate dehydrogenase complex in sperm
-
ir
ATP + [pyruvate dehydrogenase (lipoamide)]
ADP + [pyruvate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
involved in regulation of mitochondrial pyruvate dehydrogenase complex
-
ir
additional information
?
-
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms
-
-
-
additional information
?
-
-
fibrates induction of PDK4 might be coupled to an decrease in serum triglycerides and fatty acid levels which can cause protein degradation in muscles, PDK4 induction is increased in acute rhabdomyolysis
-
-
-
additional information
?
-
-
PDK regulates the pyruvate dehydrogenase multienzyme complex activity
-
-
-
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, complex regulation and the molecular mechanisms
-
-
-
additional information
?
-
-
PDK4 is critically important in the starved state because it helps prevent hypoglycemia, the enzyme is part of the pyruvate dehydrogenase complex PDC, detailed overview and modeling of the complex regulation and the molecular mechanisms
-
-
-
additional information
?
-
-
peroxisome proliferator-activated receptors and insulin have regulatory functions in expression of isozymes PDK2 and PDK4, regulation mechanism
-
-
-
additional information
?
-
-
pyruvate dehydrogenase kinase is part of the pyruvate dehydrogenase complex, regulation and component interactions, PDK2 binds the inner lipoyl domain L2, preferably in dimeric form, overview
-
-
-
additional information
?
-
-
rapid upregulation of isozyme PDK4 in skeletal muscle after prolonged exercise, PDK activity is increased during prolonged exercise, physiologic/metabolic state, overview
-
-
-
additional information
?
-
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
-
additional information
?
-
-
the PDK/PDH pathway is reduced by 73% in non small cell lung carcinoma contributing to hypoxia-inducible factor-1 stability and aerobic glycolysis
-
-
-
additional information
?
-
-
a homodimer of pyruvate dehydrogenase kinase is an integral part of the pyruvate dehydrogenase complex, PDC, to which it is anchore primarily through the inner lipoyl-bearing domains L2 of transacetylase component, binding structure, catalytic cycle of PDHK and its translocation over the PDC surface is thought to be mediated by the symmetric and asymmetric modes, in which the PDHK dimer binds to two and one L2-domain(s), respectively, overview
-
-
-
additional information
?
-
-
hypoxia-inducible factor HIF-1, inducible e.g. by CoCl2, mediates the expression of PDK1, which inhibits the pyruvate dehydrogenase in the tricarboxylic cycle by phosphorylation, high PDK1 activity increases the ATP levels and prevents hypoxia-induced reactive oxygen species generation and apoptosis
-
-
-
additional information
?
-
-
PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate, regulation of the pyruvate dehydrogenase complex, PDK4 overexpression in association with type I diabetes
-
-
-
additional information
?
-
-
PDHK2 is required for binding to the inner lipoyl domain L2 of the dihydrolipoyl acetyltransferase of the pyruvate dehydrogenase complex
-
-
-
additional information
?
-
Q15118
PDK isozymes are molecular switches that downregulate the pyruvate dehydrogenase complex PDC by reversible phosphorylation in mitochondria, L2 domain binding structure of isozyme PDK3, overview
-
-
-
additional information
?
-
-
PDK4 expression is specifically regulated by retinoic acids, via retinoid receptors, and trichostatin A, an inhibitor of histone deacetylase
-
-
-
additional information
?
-
-
PDK4 is involved in metabolic changes after induction by high-fat/low carbohydrate diet, overview
-
-
-
additional information
?
-
-
phosphorylation of the pyruvate dehydrogenase complex PDC by the pyruvate dehydrogenase kinases PDK2 and PDK4 inhibits PDC activity, expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA, transcriptional regulation of the PDK4 gene by the estrogen-related receptors ERRalpha and ERRgamma, the ERRs are orphan nuclear receptors whose physiological roles include the induction of fatty acid oxidation in heart and muscle, overview
-
-
-
additional information
?
-
-
pyruvate dehydrogenase kinase isozymes are the molecular switch that down-regulates activity of the pyruvate dehydrogenase complex through reversible phosphorylation
-
-
-
additional information
?
-
Mus musculus C75BL/6
-
regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor, mechanism
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
dependent on
ATP
-
dependent on
ATP
-
dependent on
ATP
O02623
dependent on
ATP
-
dependent on
ATP
-
dependent on
ATP
Q63065
dependent on; dependent on
ATP
-
dependent on
ATP
-
causes a decrease in PDHK2 affinity for the L2 domain
ATP
-
; ordered reaction mechanism with ATP
ATP
-
binding site structure, involves Gly317 and Tyr320, and K+ ions
ATP
-
L2 binding increases affinities for both ADP and ATP
ATP
-
binding kinetics, ATP or ADP plus pyruvate at low concentration of about 0.1 mM cause PDHK2 dimer to associate to a tetramer. These changes make major contributions to synergistic inhibition of PDHK2 activity by ADP and pyruvate, overview
ATP
-
the ATP-binding loop in one PDHK3 subunit adopts an open conformation, implying that the nucleotide loading into the active site is mediated by the inactive pre-insertion binding mode
ATP
C1IHT9
-
ATP
Q16654
binding structure with isozyme PDK4, detailed overview
ATPgammaS
-
dissociation constants as ATP in binding to PDK3
additional information
-
no activation by cAMP
-
additional information
-
no activation by cAMP; no activation by cGMP
-
additional information
-
no activation by Ca2+/calmodulin or calmodulin alone; no activation by cAMP; no activation by cGMP
-
additional information
-
no activation by succinyl-CoA, tiglyl-CoA, crotonyl-CoA, glutaryl-CoA, DL-3-hydroxy-3-methylglutaryl-CoA, acetylcarnitine or 3-hydroxybutyryl-CoA
-
additional information
-
no activity with GTP
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cl-
-
activates; required for stimulation of PDK2 by reduction and reductive acetylation of E2
Divalent cations
-
requirement
K+
-
inhibits in presence of ADP
K+
-
K+-dependent activation, inhibited by thiamine diphosphate
K+
-
2.2fold activation at 20 mM K+, not pH- and buffer concentration-dependent
K+
Q16654
activation
K+
-
activates; required for stimulation of PDK2 by reduction and reductive acetylation of E2
K+
-
binds via Gly319, involved in inhibition by ADP, Nov3r, and AZ12, and in binding of ATP
K+
-
activates, the Km for ATP is decreased and ADP inhibition is enhanced by elevating K+ ion levels, ligand-induced changes in K+ binding, overview
Mg2+
-
actual substrate: MgATP2-; requirement
Mg2+
-
actual substrate: MgATP2-; requirement
Mg2+
-
requirement
Mg2+
-
requirement
Mg2+
-
actual substrate: MgATP2-; requirement
Mg2+
-
requirement
Mg2+
-
-
Mg2+
Q63065
;
Mg2+
-
-
Mg2+
-
required
Mg2+
-
required
Na+
-
hinders interaction between PDK2 and the inner lipoyl domain L2
NH4+
-
activation in the absence of ADP, inhibits in presence of ADP
phosphate
-
activates
Mn2+
-
can replace Mg2+ to some extent; requirement
additional information
-
no activation by Ca2+
additional information
-
no activation by NaCl, LiCl
additional information
-
no activation by Na+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-3,3,3-trifluoro-2-hydroxy-2-methylpropioamide
-
strong inhibition, isozymes PDK1 and PDK2, inhibition mechanism
2-Chloroisohexanoate
-
weak
2-oxobutyrate
-
-
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
Q16654
inhibitor M77976 binds to the ATP-binding pocket of PDK4 and causes local conformational changes with complete disordering of the ATP lid. M77976 binding also leads to a large domain rearrangement that further expands the active-site cleft of PDK4 compared with the ADP- and AMPPNP-bound forms
adenosine 5'-[beta,gamma,imido]triphosphate
-
isozymes PDK1 and PDK2, inhibition mechanism
adenosine 5'-[beta,gamma-imido]triphosphate
-
-
ADP
-
competitive to ATP
ADP
-
competitive to ATP; inhibition only in the presence of monovalent cations; Mg2+ does not protect
ADP
-
competitive to ATP; inhibition only in the presence of monovalent cations
ADP
-
competitive to ATP; inhibition only together with pyruvate, kinetics; synergism with pyruvate
ADP
Q63065
competitive to ATP; isozyme PDK2, wild-type and mutants G284A and G319A
ADP
-
50-60% inhibition of isozyme PDK3, in presence of dihydrolipoyl transacetylase 70%
ADP
-
-
ADP
-
isozyme PDK3: synergistic with phosphate; isozyme PDK4: K+ and dichloroacetate increase the inhibitory effect; synergism with pyruvate
ADP
Q63065
recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate; recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate
ADP
-
synergism with pyruvate
ADP
-
isozyme PDK2: synergistic with phosphate; synergism with pyruvate
ADP
-
synergism with pyruvate
ADP
-
product inhibition, competitive to ATP, synergistic with pyruvate, PDK2, ADP, and pyruvate form a dead-end complex
ADP
-
binding site structure, involves Gly319 and Phe318, and K+ ions
ADP
-
product inhibition, L2 binding increases affinities for both ADP and ATP
ADP
-
product inhibition, synergistic with pyruvate
ADP
-
binding kinetics,ATP or ADP plus pyruvate at low concentration of about 0.1 mM cause PDHK2 dimer to associate to a tetramer. These changes make major contributions to synergistic inhibition of PDHK2 activity by ADP and pyruvate, overview
ADP
-
synergism with dichloroacetate
ADP
-
inhibition only in the presence of monovalent cations
ATP
-
above 0.5 mM, substrate inhibition, only in the presence of K+, Mg2+ does not protect
AZ12
-
i.e. N-[4-([ethylanilino]sulfonyl)2-methylphenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, binding structure, requires K+ for inhibition
AZD7545
-
noncompetitive to ATP
-
AZD7545
-
noncompetitive to ATP, IC50 values for isozymes PDHK1, PDHK2, and PDHK4
-
AZD7545
-
compound AZD7545 disrupts the interactions between PDHK2 and L2 and thereby inhibits PDHK2 activity
-
AZD7545
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
-
AZD7545
-
structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview, when the E2p/E3BP core is absent, AZD7545 stimulates scaffold-free basal PDK1 and PDK3 activities to 1.3fold and 10fold, respectively
-
Butyryl-CoA
-
at high concentrations
CaCl2
-
no inhibition
CaCl2
-
-
Chymotrypsin
-
proteolysis of kinase alpha-, not beta-subunit, no inactivation by trypsin-mediated proteolysis of beta-subunit
-
Cl-
-
40% inhibition at 80 mM, K+-independent inhibition
CoA
-
-
compound K
-
noncompetitive to ATP, IC50 values for isozymes PDHK1, PDHK2, and PDHK4
compound K
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor
decanoyl-CoA
-
-
Dichloroacetate
-
noncompetitive; pyruvate analog, synergism with ADP, K+ or phosphate, kinetics
Dichloroacetate
-
potent and highly specific synthetic allosteric inhibitor mimicking pyruvate, inhibition mechanism
Dichloroacetate
-
inhibition of isozyme PDK3 is independent of dihydrolipoyl transacetylase, while isozyme PDK2 is more sensitive to inhibition when bound to it
Dichloroacetate
-
-
Dichloroacetate
-
isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK4: ADP, K+ and Cl- increase the inhibitory effect
Dichloroacetate
Q63065
recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate; recombinant homodimers of PDK1 and PDK2 and heterodimers of PDK1 + PDK2, synergism with dichloroacetate
Dichloroacetate
Q63065
highly specific
Dichloroacetate
-
noncompetitive to ATP
Dichloroacetate
-
binds at the pyruvate binding site, binding structure, involves e.g. Arg154
Dichloroacetate
-
R114, S83, I157 and, to some extent, H115 are essential for DCA binding by PDHK, Y80 and D117 are required for the communication between the dichloroacetate-binding site and active site of PDHK2, overview
Dichloroacetate
-
binding kinetics
Dichloroacetate
-
synergism with ADP, binding promotes conformational changes at the active-site cleft, structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview
Dichloroacetate
-
-
Dichloroacetate
-
the PDK inhibitor restores pyruvate dehydrogenae activity and enhances glucose oxidation with beneficial molecular effects, i.e. downregulation of FOXO-1 and PDK4, and functional improvement,i.e. enhanced right ventricular function and exercise capacity
dichloroacetophenone
-
isozymes PDK1 and PDK2, inhibition mechanism
Dihydrolipoic acid
-
inhibits the activity of PDK3 towards the reconstituted PD complex slightly, but the activity towards E1 alone completely, inhibition mechanism
Dihydrolipoic acid
-
inhibits the activity of PDK1 towards the reconstituted PD complex, inhibition mechanism
Disulfides
-
thiols reverse
DTNB
-
most potent at 0.001 mM
DTNB
-
-
H2O2
-
PDHK2 activity is inhibited by low levels of hydrogen peroxide generated by the respiratory chain via reversible oxidation of Cys45 and Cys392 on PDHK2
Hexanoyl-CoA
-
-
HPO42-
-
enhances inhibition by pyruvate or dichloroacetate
HPO42-
-
noncompetitive to ATP in the range of 1-10 mM; within physiological range, only in the presence of K+, not in its absence
Insulin
-
blockage of the expression of isozyme PDK4 via insulin-activated pathway
-
Insulin
-
decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma
-
K+
-
synergism with ADP
K+
-
pyruvate or dichloroacetate
lactone derivative of dichloroacetophenone
-
isozymes PDK1 and PDK2, inhibition mechanism
Linolenoyl-CoA
-
-
linoleoyl-CoA
-
-
menadione
-
PDHK2 activity is inhibited via reversible oxidation of Cys45 and Cys392 on PDHK2
myristoyl-CoA
-
-
Na+
-
above 50 mM, alone and synergism with ADP
NAD+
-
-
Nov3r
-
i.e. (4-[(2,5)-dimethyl-4-(3,3,3-trifluoro-2-hydroxy-2-methyl-propanoyl)piperazinyl]carbonyl)benzonitrile, binding structure, requires K+ for inhibition
Nov3r
-
an amide of trifluoro-2-hydroxy-2-methylpropionic acid, a tight binding inhibitor, a mimic of the acetyl-dihydrolipoyl group, inhibits PDK2
oleoyl-CoA
-
-
oximes of triterpenes
-
with 17beta hydroxyl and abietane derivatives, several, overview
-
P53
-
negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2
Pfz3
-
i.e. N-(2-aminoethyl)-2-(3-chloro-4-[(4-isopropylbenzyl)oxy]phenyl)acetamide, binding site structure, involves e.g. the R domain, allosteric inhibition mechanism, overview
phosphate
-
enhances inhibition by pyruvate
phosphate
-
isozyme PDK2, synergistically with ADP and pyruvate
Pyruvamide
-
inhibition of isozymes PDK1, PDK2, and PDK4
pyruvate
-
-
pyruvate
-
kinetics; noncompetitive to ATP; synergism with ADP; synergism with K+ or phosphate
pyruvate
-
dead-end inhibitor; kinetics; noncompetitive to ATP; synergism with ADP
pyruvate
-
isozyme PDHK4 is less sensitive than PDHK1 and PDHK2
pyruvate
-
synergism with ADP
pyruvate
-
inhibits at concentrations above 0.1 mM, activates below 0.05 mM; isozyme PDK2: ADP and K+ increase the inhibitory effect; isozyme PDK3; synergism with ADP
pyruvate
-
very weak inhibition
pyruvate
-
isozyme PDK2: synergistic with phosphate; isozyme PDK3; very weak inhibition
pyruvate
-
very weak inhibition
pyruvate
-
product inhibition, synergistic with ADP, PDK2, ADP, and pyruvate form a dead-end complex
pyruvate
-
slight product inhibition, synergistic with ADP
pyruvate
-
product inhibition, synergistic with ADP
pyruvate
-
-
pyruvate
-
binding kinetics,ATP or ADP plus pyruvate at low concentration of about 0.1 mM cause PDHK2 dimer to associate to a tetramer. These changes make major contributions to synergistic inhibition of PDHK2 activity by ADP and pyruvate, overview
pyruvate
-
Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
pyruvate
-
-
R-lipoic acid
-
inhibits isozyme PDK3 activity in the reconstituted PD complex, but not towards E1 alone, inhibition mechanism
R-lipoic acid
-
inhibits isozymes PDK1, PDK2, and PDK4 activities in the reconstituted PD complex and towards E1 alone, inhibition mechanism, overview
radicicol
-
binding site structure, structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview
radicicol
Q16654
-
Rapamycin
-
inhibits PDK2 and PDK4, has no effect on insulin-caused downregulation of the isozymes
S-lipoic acid
-
inhibits isozyme PDK3 activity in the reconstituted PD complex, but not towards E1 alone, inhibition mechanism
S-lipoic acid
-
inhibits isozymes PDK1, PDK2, and PDK4 activities in the reconstituted PD complex and towards E1 alone, inhibition mechanism, overview
SO42-
-
with the same effect as HPO42-
stearoyl-CoA
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
2-oxoisopentanoate protects, not pyruvate; non- or uncompetitively inhibition of K+-stimulated activity
thiamine diphosphate
-
kinetics; non- or uncompetitively inhibition of K+-stimulated activity
thiamine diphosphate
-
in the presence of pyruvate
thiamine diphosphate
-
-
triterpenes
-
isozymes PDK1 and PDK2, inhibition mechanism
-
MnCl2
-
-
additional information
-
no inhibition by 2-oxoglutarate; no inhibition by cAMP
-
additional information
-
no inhibition by cAMP; no inhibition by cGMP
-
additional information
-
no inhibition by cAMP; no inhibition by cGMP; not affected by calmodulin with or without Ca2+
-
additional information
-
no inhibition by succinyl-CoA, tiglyl-CoA, crotonyl-CoA, glutaryl-CoA, DL-3-hydroxy-3-methylglutaryl-CoA, acetylcarnitine or 3-hydroxybutyryl-CoA
-
additional information
-
increase of ionic strength inhibits, changes of osmolarity of assay medium do not affect activity
-
additional information
-
carnitine, acetylcarnitine, malate, spermine, and calcium have no effect on isozyme PDK3 in presence of dihydrolipoyl transacetylase
-
additional information
-
-
-
additional information
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms; the effects of mono- and divalent ions vary greatly between the isozymes
-
additional information
-
-
-
additional information
-
isozyme PDK3 undergoes self-association in absence of dihydrolipoyl transacetylase domain L2 leading to a decrease in activity; starvation and diabetes reduce the expression of isozyme PDK2
-
additional information
-
insulin regulate the basal expression level of PDK4 by inhibiting the glucocorticoid-dependent stimulation of PDK4 expression via inactivation of FOXO proteins, FOXO proteins bind to the insulin response element which is required for the glucocorticoid response
-
additional information
-
effects of recombinant E2 component-derived deletion constructs on PDK activity, overview
-
additional information
-
isozyme-specific inhibition by AZD7545 analogues
-
additional information
-
insulin reverses the stimulation effect of reduced glucose levels increasing expression levels of PDK2 and PDK4, insulin alone decreases the enzyme expression levels below basal values, insulin effects on the enzyme are inhibited by phosphoatidyl 3-kinase inhibitors wortmannin and LY294002, i.e. 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
additional information
-
pyruvamide is a poor inhibitor of PDK3
-
additional information
-
high-fat diet with unaltered n-3 fatty acid levels leads to increase in PDK activity and decrease in PDH activity, high-fat diet with elevated levels of n-3 fatty acids attenuates the increase in PDH kinase activity and decreases PDH activity, overview
-
additional information
-
PDK2 inhibition mechanism, overview
-
additional information
-
insulin downregulates expression of PDK4, but not of PDK2, after high-fat and control diets, but does not regulate the PDK4 protein
-
additional information
-
inhibition of FGFR1 by a small molecule inhibitor TKI258 results in decreased tyrosine phosphorylation levels of GST-PDHK1 and reduced PDHK1 activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-oxoisopentanoate
-
only in the presence of K+ and thiamine diphosphate, kinetics
2-oxoisopentanoate
-
-
acetoacetyl-CoA
-
slight activation
acetyl-CoA
-
high stimulation through acetylation of the transacetylase-catalyzing inner core portion of the dihydrolipoyl acetyltransferase; involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
acetyl-CoA
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
acetyl-CoA
O02623
kinase bound to transacetylase core; synergism with NADH
acetyl-CoA
-
kinase bound to transacetylase core; synergism with NADH
acetyl-CoA
-
domain-specific binding, isozymes PDK2 and PDK3; synergism with NADH
acetyl-CoA
-
synergism with NADH
acetyl-CoA
-
synergism with NADH
acetyl-CoA
-
isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect; synergism with NADH
acetyl-CoA
-
domain-specific binding, isozymes PDK2 and PDK3
acetyl-CoA
-
activates the enzyme, especially isozyme PDK2; domain-specific binding, isozymes PDK2 and PDK3
acetyl-CoA
-
stimulation by acetyl-CoA requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview
acetyl-CoA
-
Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
acetyl-CoA
-
-
AZD7545
-
structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview, when the E2p/E3BP core is absent, AZD7545 stimulates scaffold-free basal PDK1 and PDK3 activities to 1.3fold and 10fold, respectively
-
benzoyl-CoA
-
slight activation
dibutyryl cAMP
-
in muscle, reversed by insulin
Dihydrolipoyl transacetylase
-
rate-limiting in the holo-complex
-
Dihydrolipoyl transacetylase
-
3-5fold stimulation
-
Dihydrolipoyl transacetylase
-
pyruvate dehydrogenase-complex transacetylase core
-
Dihydrolipoyl transacetylase
-
binding and activation mechanism; involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
-
Dihydrolipoyl transacetylase
-
-
-
Dihydrolipoyl transacetylase
O02623
pyruvate dehydrogenase-complex transacetylase core
-
Dihydrolipoyl transacetylase
-
pyruvate dehydrogenase-complex transacetylase core
-
Dihydrolipoyl transacetylase
-
lipoylation is required for binding, structural mutants stimulate less; stimulation rates in different buffers, stimulating domains for the isozyme PDK2 and PDK3 differ, overview
-
Dihydrolipoyl transacetylase
-
requirement
-
Dihydrolipoyl transacetylase
-
-
-
Dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes
-
Dihydrolipoyl transacetylase
-
acts as a direct allosteric agent in altering the regulatory kinase activity, serves as an anchoring scaffold; degree of interaction and mechanism differ for the 4 different isozymes
-
Dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes
-
Dihydrolipoyl transacetylase
-
activation depends on the buffer system, the isozyme and the reduction status of the lipoyl groups; activation in presence of a binding protein, referred to as dihydrolipoamide dehydrogenase-binding protein; degree of interaction and mechanism differ for the 4 different isozymes
-
Dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes
-
Dihydrolipoyl transacetylase
-
activation depends on the buffer system, the isozyme and the reduction status of the lipoyl groups; activation in presence of a binding protein, referred to as dihydrolipoamide dehydrogenase-binding protein; degree of interaction and mechanism differ for the 4 different isozymes
-
Dihydrolipoyl transacetylase
-
isozyme PDK2, activation mechanism, binding structure
-
Dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes; dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism
-
Dihydrolipoyl transacetylase
-
binding and activation mechanism; degree of interaction and mechanism differ for the 4 different isozymes; domaine-specific binding, isozymes PDK2 and PDK3, the latter binding more tightly to the L2 domain; dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism; isozyme PDK2 can phosphorylate free pyruvate dehydrogenase complex but bound dihydrolipoyl transacetylase enhances the rate up to 5000fold
-
Dihydrolipoyl transacetylase
-
degree of interaction and mechanism differ for the 4 different isozymes; dynamic, effector-modified interactions of the regulatory isozymes with the flexibly held outer domains of the core-forming dihydrolipoyl acetyl transferase component of pyruvate dehydrogenase complex to adapt the complex activity, regulatory mechanism
-
free fatty acids
-
leads to overexpression of isozyme PDK4 via mechanism involving peroxisome proliferator-activated receptor-alpha
-
glucocorticoids
-
leads to overexpression of isozyme PDK4 via mechanism involving peroxisome proliferator-activated receptor-alpha
-
glucocorticoids
-
regulate the basal expression level of PDK4, bind to a glucorticoid response element GRE located in the proximal promotor requiring binding of FOXO proteins, FOXO protein binding to the GRE can be inhibited by insulin, glucocorticoids act synergistically with retinoic acid
-
inner lipoyl-bearing domain 2
-
i.e. L2, binding to the inner lipoyl domain L2 of E2 component of the PDC enzyme complex activates and regulates the enzyme by conformational changes and disrupting the ATP lid and eliminating product inhibition by ADP, mechanism, L2 binding strongly decreases PDHK2 affinity for ATP, strongest activation occurrs in presence of E1, E1-binding domain, and E2, overview
-
L-methylmalonyl-CoA
-
slight activation
L2 domain
-
inner lipoyl domain of the E2 component of PDC, activates PDK2
-
L2 domain of pyruvate dehydrogenase complex
-
binding to the inner lipoyl domains L2 of E2 component activate the enzyme by conformational changes and disrupting the ATP lid and eliminating product inhibition by ADP, binding structure, overview, L2 binding increases affinities for both ADP and ATP
-
Lipid
-
selective increase in amount of isozyme PDHK4 protein in both hyperthyroidism and high-fat feeding
Lipid
-
in muscle, reversed by insulin
Lipid
-
enhance expression of hepatic isozyme PDK2 during high-fat feeding
lipoyl domain L2
-
L2 of the PDK3-containing pyruvate dehydrogenase complex induces a cross-tail conformation in PDK3, resulting in an opening of the active site cleft and the stimulation of kinase activity
-
NADH
-
activation, in the presence of K+
NADH
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
NADH
-
involved in the regulation of enzyme activity regulating pyruvate dehydrogenase complex
NADH
O02623
kinase bound to transacetylase core; synergism with acetyl-CoA
NADH
-
kinase bound to transacetylase core; synergism with acetyl-CoA
NADH
-
domain-specific binding, isozymes PDK2 and PDK3; synergism with acetyl-CoA
NADH
-
isozyme PDK2: addition of K+ and Cl- required, phosphate increases the stimulating effect
NADH
-
domain-specific binding, isozymes PDK2 and PDK3
NADH
-
activates the enzyme, especially isozyme PDK2; domain-specific binding, isozymes PDK2 and PDK3
NADH
-
stimulation by NADH requires both K+ and at least one anion, phosphate or chloride, mechanisms for stimulation of PDK2, via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation, overview
NADH
-
Pdk2-specific activity increases if acetyl-CoA and NADH levels increase, but decreases if pyruvate levels increase
NADH
-
activation, in the presence of K+; activation, in the presence of NH4+
Octanoate
-
in muscle, reversed by insulin
oleate
-
activates PDK2 and PDK4 nearly 2fold at 0.1 mM, not synergistic with palmitate, stimulation is completely inhibited by insulin at 0.001 mM
palmitate
-
activates PDK2 and PDK4 nearly 2fold at 0.1 mM, not synergistic with oleate, stimulation is completely inhibited by insulin at 0.001 mmM
peroxisome proliferator-activated receptor-alpha
-
involved in mechanism to enhance expression of isozyme PDK4, but not isozyme PDK2, during starvation
-
phosphate
-
isozyme PDK43, direct inhibition and elevation of the Km for ATP
propionyl-CoA
-
slight activation at low concentrations, synergism with NADH plus NAD+
pyruvate
-
at low concentration, with the thiamine diphosphate containing pyruvate dehydrogenase complex, stimulation mechanism
pyruvate
-
-
pyruvate
-
inhibits at concentrations above 0.1 mM, activates below 0.05 mM, dependent on thiamine diphosphate
Thyroid hormones
-
selective increase in amount of isozyme PDHK4 protein in both hyperthyroidism and high-fat feeding
-
WY-14,643
-
activator of peroxisome proliferator-activated receptor-alpha; in gastrocnemius muscle, specifically increases PDK4 expression
WY-14,643
-
activator of peroxisome proliferator-activated receptor-alpha; in liver, specifically increases PDK4 expression
malonyl-CoA
-
-
additional information
-
model of specific interactions and signal translation within the pyruvate dehydrogenase complex and between pyruvate dehydrogenase kinase and subunits, differences between the isozymes, mechanisms
-
additional information
-
-
-
additional information
-
during hyperthyroidism, the expression of hepatic isozymes PDK2 and PDK4 is increased; starvation increases expression of isozyme PDK4
-
additional information
-
starvation increases expression of isozyme PDK4
-
additional information
-
histone acetylation and transcription activation of gene PDK4 by retinoic acid and trichostatin A, retinoic acid acts synergistically with glucocorticoids, induction by dexamethasone can be inhibited by RU486
-
additional information
-
no effects on PDK4 expression level by dexamethasone
-
additional information
-
glucocorticoids and insulin regulate the basal expression level of PDK4, starvation and diabetes mellitus increase PDK4 expression in most tissues, no effects by dexamethasone
-
additional information
-
farnesoid X receptor agonists stimulate PDK4 expression in hepatocytes in vitro
-
additional information
-
farnesoid X receptor agonist GW4064 stimulates PDK4 expression in liver in vivo
-
additional information
-
glucocorticoids and farnesoid X receptor agonists, dexamethasone or WY14643, stimulate PDK4 expression in hepatoma cells in vitro
-
additional information
-
effects of recombinant E2 component-derived deletion constructs on PDK activity, overview
-
additional information
-
the enzyme is stimulated 3.45fold by NADH/NAD+ and/or acetyl-Co via reduction and reductive acetylation of the lipoyl moieties of pyruvate dehydrogenase complex component E2 dihydrolipoyl acetyltransferase requiring elevated levels of Cl- and K+, activation increases the kcat and Km for ATP
-
additional information
-
PDK4 mRNA is very rapidly induced by fibrates, e.g. bezafibrate, and statins, e.g. statin, pravastatin, or simvastatin, and anti-bacterial drugs, e.g. quinolon, ofloxacin, and norfloxacin, in a tissue-specific manner, overview
-
additional information
-
agonist activation of peroxisome proliferator-activated receptors alpha and delta specifically upregulates PDK4 transcription, while activation of peroxisome proliferator-activated receptor gamma specifically downregulates PDK2 transcription, reduced glucose levels increase expression levels of PDK2 and PDK4, the stimulation effect is reversed by insulin, insulin alone decreases the enzyme expression levels below basal values
-
additional information
-
the enzyme is stimulated by reduction or reduction/acetylation of the lipoyl moieties of pyruvate dehydrogenase complex component E2
-
additional information
-
fasting largely increases PDK4 expression, increases PDK3 expression, but effects PDK2 and PDK1 only slightly in skeletal muscle, overview, peroxisome proliferator-activated receptor-alpha PPAR-alpha protein and forkhead homologue FKHR in rhabdomyosarcoma are putative transcriptional activators of the enzyme
-
additional information
-
rapid upregulation of isozyme PDK4 in skeletal muscle after prolonged exercise, PDK activity is increased 2.5fold during 240 min of exercise
-
additional information
-
PDK4 expression is induced by hepatic nuclear factor 4, HNF4, determination of binding sites on the PDK4 promoter
-
additional information
-
E2-dependent PDHK2 activation, molecular modeling and mechanism
-
additional information
-
PDK4 expression is induced by retinoic acids and trichostatin A
-
additional information
-
hypoxia-inducible factor HIF-1 induces PDK1 expression, PDK1 is a direct target gene of HIF-1
-
additional information
-
the peroxisome proliferator-activated receptor gamma coactivator, PGC-1gamma, as well as estrogen-related receptors ERRalpha and ERRgamma stimulate the expression of isozymes PDK2 and PDK4, the latter being inhibited by insulin, expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA, overview
-
additional information
-
PDK4 expression is 2fold induced in high-fat/low carbohydrate diet and is blunted under basal and clamp conditions after high-fat diet, overview
-
additional information
-
expression of isozymes PDK2 and PDK4 is induced by free fatty acids, overview
-
additional information
-
tyrosine phosphorylation enhances PDHK1 kinase activity by promoting ATP and pyruvate dehydrogenase complex binding
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.006
ATP
-
isozyme PDK2, 30C, pH 7.3, MOPS-K+ buffer; isozyme PDK3, 30C, pH 7.3, Tris-HEPES buffer
0.007
ATP
Q63065
recombinant His-tagged isozyme PDK2, 37C, pH 7.8
0.0077
ATP
-
pH 7.4, 30C, with oxidized E2
0.01
ATP
-
at 0.2 M buffer concentration
0.0109
ATP
-
pH 7.4, 30C, with oxidized E2, in presence of NADH/NAD+
0.0113
ATP
-
pH 7.4, 30C, with oxidized E2, in presence of 2 mM DTT
0.013
ATP
-
isozyme PDK3, 30C, pH 7.3, MOPS-K+ buffer
0.016
ATP
Q63065
37C, recombinant isozyme PDK2 wild-type
0.02
ATP
-
kidney enzyme; pH 7.5, 30C; pyruvate dehydrogenase complex
0.02
ATP
-
kidney enzyme; pH 7.0, 30C; pyruvate dehydrogenase complex
0.02
ATP
-
pH 7.5, 25C
0.023
ATP
-
isozyme PDK2, 30C, pH 7.3, Tris-HEPES buffer
0.025 - 0.22
ATP
-
pH 7.4, 30C, PDK2, with substrate E2-bound E1, dependent on the assay conditions concerning buffer composition, overview
0.025
ATP
-
-
0.025
ATP
-
at 0.04 M buffer concentration
0.026
ATP
-
-
0.028
ATP
Q63065
37C, recombinant mutant G284A of isozyme PDK2
0.029
ATP
-
isozyme PDK3, 30C, pH 7.3, phosphate buffer
0.034
ATP
Q63065
recombinant His-tagged isozyme PDK1, 37C, pH 7.8
0.039
ATP
-
pH 7.4, 30C, with reduced E2
0.04
ATP
-
isozyme PDK2, 30C, pH 7.3, phosphate buffer
0.047
ATP
-
pH 7.4, 30C, with reduced E2, in presence of NADH/NAD+
1.16
ATP
-
pH 7.4, 30C, with reduced E2, in presence of NADH/NAD+ and acetyl-CoA
1.5
ATP
Q63065
37C, recombinant mutant G319A of isozyme PDK2
0.02
Mg2+
-
kidney enzyme; pH 7.5, 30C; pyruvate dehydrogenase complex
0.02
Mg2+
-
kidney enzyme; pH 7.0, 30C; pyruvate dehydrogenase complex
0.0006
Pyruvate dehydrogenase
-
in presence of dihydrolipoyl transacetylase; pH 7.5, 30C
-
0.0006
Pyruvate dehydrogenase
-
in presence of dihydrolipoyl transacetylase; pH 7.0, 30C
-
0.02
Pyruvate dehydrogenase
-
in absence of dihydrolipoyl transacetylase; pH 7.5, 30C
-
0.02
Pyruvate dehydrogenase
-
in absence of dihydrolipoyl transacetylase; pH 7.0, 30C
-
0.05
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant L234H; pH 7.5, 37C, recombinant wild-type PDK
-
0.075
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant L234A
-
0.2
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant H233A
-
0.28
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant E238A
-
0.4
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant E238Q
-
3.5
Pyruvate dehydrogenase
-
about, pH 7.5, 37C, recombinant PDK mutant E238H
-
0.02
Mg2+
-
-
additional information
additional information
-
the Km value for ADP depends on the presence and concentration of K+, effect of K+ on kinetic parameters
-
additional information
additional information
-
changes in ionic strength
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
dissociation constants for ADP and ATP binding, L2 binding increases affinities for both ADP and ATP
-
additional information
additional information
-
pyruvate dehydrogenase complex components interaction dissociation constants and kinetics
-
additional information
additional information
-
binding of wild-type and mutant PDHK2 proteins to the unaltered L2 domain, kinetics
-
additional information
additional information
-
kinetics and thermodynamics of PDK binding to L2 within the pyruvate dehydrogenase complex
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.12
ATP
-
pH 7.4, 30C, with oxidized E2
0.17
ATP
-
pH 7.4, 30C, with oxidized E2, in presence of 2 mM DTT
0.21
ATP
-
pH 7.4, 30C, with oxidized E2, in presence of NADH/NAD+
0.512
ATP
-
-
0.533
ATP
-
-
0.9 - 4.7
ATP
-
pH 7.4, 30C, PDK2, with substrate E2-bound E1, dependent on the assay conditions concerning buffer composition, overview
0.91
ATP
-
pH 7.4, 30C, with reduced E2
1.3
ATP
-
pH 7.4, 30C, with reduced E2, in presence of NADH/NAD+
3.15
ATP
-
pH 7.4, 30C, with reduced E2, in presence of NADH/NAD+ and acetyl-CoA
0.0004
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant E238A
-
0.0005
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant E238H
-
0.0014
Pyruvate dehydrogenase
-
PDK activity in skeletal muscle after short 10 min or no exercise
-
0.0032
Pyruvate dehydrogenase
-
PDK activity in skeletal muscle after prolonged exercise of 240 min
-
0.07
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant L234A
-
0.28
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant H233A
-
0.39
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant PDK mutant L234H
-
0.55
Pyruvate dehydrogenase
-
pH 7.5, 37C, recombinant wild-type PDK
-
0.0383
[Pyruvate dehydrogenase (lipoamide)]
-
phosphorylation site 3 of subunit E1, isozyme PDK1, pH 7.0, 30C
-
0.0933
[Pyruvate dehydrogenase (lipoamide)]
-
phosphorylation site 2 of subunit E1, isozyme PDK3, pH 7.0, 30C
-
0.108
[Pyruvate dehydrogenase (lipoamide)]
-
phosphorylation site 2 of subunit E1, isozyme PDK4, pH 7.0, 30C
-
0.11
[Pyruvate dehydrogenase (lipoamide)]
-
phosphorylation site 1 of subunit E1, isozyme PDK1, pH 7.0, 30C
-
0.277
[Pyruvate dehydrogenase (lipoamide)]
-
phosphorylation site 1 of subunit E1, isozyme PDK2, pH 7.0, 30C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0031
adenosine 5'-[beta,gamma-imido]triphosphate
-
pH 7.4, 30C, versus ATP
0.1
ADP
-
pH 7.5, 30C
0.14 - 0.52
ADP
-
pH 7.4, 30C, versus ATP, dependent on the assay conditions concerning buffer composition, overview
0.2
ADP
Q63065
37C, recombinant isozyme PDK2 wild-type
0.21
ADP
-
pH 7.5, 25C
0.3
ADP
Q63065
37C, recombinant mutant G284A of isozyme PDK2
1.6
ADP
Q63065
37C, recombinant mutant G319A of isozyme PDK2
0.2
Dichloroacetate
-
pH 7.4, 37C
0.2
Dichloroacetate
-
isozyme PDHK2, 30C
0.27
Dichloroacetate
-
kinetic constant from binding study; pH 7.2, 30C
0.5
Dichloroacetate
-
isozyme PDHK4, 30C
1
Dichloroacetate
-
isozyme PDHK1, 30C
0.27
pyruvate
-
kinetic constant from binding study; pH 7.2, 30C
0.325
pyruvate
-
pH 7.5, 25C
10
HPO42-
-
pH 7.8, 30C
additional information
additional information
-
Ki value for ADP depends on the presence and concentration of monovalent cations, e.g. NH4+ or K+
-
additional information
additional information
-
inhibition kinetics for thiamine diphosphate
-
additional information
additional information
-
-
-
additional information
additional information
-
isozyme PDK4: K+ reduces the Ki for ADP and therefor enhances the inhibitory affect
-
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
-
dichloroacetate inhibition kinetics and EC50 values with wild-type and mutant PDHK2s
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.648
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
Q16654
pH 8.0, temperature not specified in the publication
0.087
AZD7545
-
pH 7.5, 25C, inhibition of isozyme PDK1
-
0.6
AZD7545
-
pH 7.5, 25C, inhibition of isozyme PDK3
-
0.013
Dichloroacetate
-
recombinant isozyme PDHK2 mutant I157A
0.29
Dichloroacetate
-
wild-type enzyme, apparent IC50 for basal activity
0.48
Dichloroacetate
-
wild-type enzyme, apparent IC50 for E2p/E3BP-dependent activity
1.2
Dichloroacetate
-
recombinant isozyme PDHK2 mutant R112A
1.7
Dichloroacetate
-
recombinant isozyme PDHK2 mutant R154A
2
Dichloroacetate
-
recombinant isozyme PDHK2 mutant R158A
2.3
Dichloroacetate
-
recombinant wild-type isozyme PDHK2
2.7
Dichloroacetate
-
recombinant isozyme PDHK2 mutant I161A
3.04
Dichloroacetate
-
mutant Y145F, apparent IC50 for basal activity
3.24
Dichloroacetate
-
mutant Y145F, apparent IC50 for E2p/E3BP-dependent activity
8.4
Dichloroacetate
-
recombinant isozyme PDHK2 mutant H115A
17.1
Dichloroacetate
-
recombinant isozyme PDHK2 mutant L53A
17.9
Dichloroacetate
-
recombinant isozyme PDHK2 mutant I111A
35.3
Dichloroacetate
-
mutant D382A/W383A, apparent IC50 for E2p/E3BP-dependent activity
37.9
Dichloroacetate
-
mutant D382A/W383A, apparent IC50 for basal activity
86.3
Dichloroacetate
-
mutant Y145F/R149A, apparent IC50 for E2p/E3BP-dependent activity
98.7
Dichloroacetate
-
mutant R149A, apparent IC50 for basal activity
102
Dichloroacetate
-
mutant Y145F/R149A, apparent IC50 for basal activity
108
Dichloroacetate
-
mutant R149A, apparent IC50 for E2p/E3BP-dependent activity
0.23
radicicol
-
pH 7.5, 25C, inhibition of isozyme PDK1
0.4
radicicol
-
pH 7.5, 25C, inhibition of isozyme PDK3
1.079
radicicol
Q16654
pH 8.0, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.006
-
PDK3 activity with E1
0.008
Q16654
purified recombinant enzyme
0.018
-
purified dihydrolipoyl transacetylase-protein X-pyruvate dehydrogenase kinase subcomplex
0.02
-
about, with E2 bound to E1, 0.2 mM ATP
0.027
-
PDK2 activity with E1
0.03
-
about, with E2 bound to E1 in presence of NADH/NAD+ and acetyl-CoA, 0.2 mM ATP
0.031
-
PDK1 activity with E1
0.032
-
PDK4 activity with E1
0.037
-
about, with free E2, 0.2 mM ATP
0.038
-
PDK4 activity with reconstituted PDC
0.045
Q64536
PDHK2 mutant T302A
0.056
-
PDK1 activity with reconstituted PDC
0.064
-
PDK3 activity with reconstituted PDC
0.066
-
about, with free E2 in presence of NADH/NAD+ and acetyl-CoA, 0.2 mM ATP
0.087
-
PDK2 activity with reconstituted PDC
0.17
Q64536
PDHK2 mutant R250A
0.276
-
fed rat, purified enzyme
0.332
-
purified enzyme, in presence of dihydrolipoyl transacetylase
0.44
-
isozyme PDK3, pH 7.3, 30C
0.46
Q64536
PDHK2 mutant Y320F
0.53
Q64536
wild type PDHK2
0.69
-
isozyme PDK2, pH 7.3, 30C
0.74
-
purified recombinant enzyme, in presence of NADH and acetyl-CoA
0.92
-
purified recombinant enzyme, in presence of NADH and acetyl-CoA
1.1
-
purified isozyme PDK2
1.24
-
starved rat, purified enzyme
1.9 - 2.7
-
purified enzyme, in presence of dihydrolipoyl transacetylase, reconstituted enzyme complex
additional information
-
-
additional information
-
-
additional information
-
activity depends on the buffer system, the reduction status of the lipoyl groups and on the serine phosphorylation site of the E1 subunit of the pyruvate dehydrogenase complex used as substrate
additional information
-
PDH activity in zucker diabetic fatty rats, i.e. ZDF rats, as indicator for the degree of PDHK inhibition
additional information
-
-
additional information
-
PDK activity in different dietary states
additional information
-
pyruvate dehydrogenase complex activities of wild-type and recombinant strains
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 7.2
-
in presence of Mg2+ or Mn2+
7 - 7.4
-
assay at
7 - 7.4
-
assay at
7.2 - 8
-
broad, at 0.15 M buffer concentration
7.2
-
assay at
7.3
-
assay at
7.3
-
autophosphorylation
7.3
-
assay at
7.4
O02623
assay at
7.4
-
assay at
7.4
-
assay at
7.5
-
assay at
7.5
-
assay at, pH-dependency of wild-type and mutant PDKs, overview
7.5
-
activity assay
7.8
Q63065
assay at; assay at
7.8
-
assay at
8
Q16654
assay at
additional information
-
optimal activity within a range of 0.03 M and 0.05 M buffer concentrations
additional information
-
different buffer systems
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 8.5
-
about 50% or 60% of maximal activity at pH 5.5 and about 65% or 50% of maximal activity at pH 8.5, in the presence of Mg2+ or Mn2+, respectively
6.2 - 9
-
about half-maximal activity at pH 6.2 and 9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
Q16654
room temperature, assay at
22
-
assay at room temperature
23
-
activity assay
25
-
assay at
25
-
assay at
30
-
assay at
30
-
assay at
30
-
assay at
30
-
assay at
30
-
assay at; phosphate buffer
30
-
assay at
30
-
assay at
30
-
assay at
30
-
assay at
37
-
assay at
37
Q63065
assay at
37
Q63065
assay at; assay at
37
-
assay at, temperature-dependency of wild-type and mutant PDKs, overview
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.9
-
mature protein
7.19
C1IHT9
theoretical
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
high PDK expression
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK3
Manually annotated by BRENDA team
-
higher activity in cerebral cortex and hippocampus than in hypothalamus, pons, medulla and olfactory bulbs
Manually annotated by BRENDA team
Q1KMR4
low expression level of PDK4
Manually annotated by BRENDA team
-
post-mortem brain extracts from patients with Alzheimer disease exhibit a decrease in PDK1 expression compared with nondemented patients
Manually annotated by BRENDA team
-
myoblast cells
Manually annotated by BRENDA team
-
embryonic fibroblast cell line
Manually annotated by BRENDA team
-
in the non small cell lung tumor-supporting stroma, reduced expression of PDK1, high PDH activity
Manually annotated by BRENDA team
-
overexpression of isozyme PDK4 during starvation or diabetes, reversible by insulin
Manually annotated by BRENDA team
-
hepatoma cell line, determination of PDK4 expression level in presence or absence of farnesoid X receptor agonists
Manually annotated by BRENDA team
-
appearance of isozyme PDK1 is limited to the heart, isozyme PDK2
Manually annotated by BRENDA team
-
developing and adult heart, the latter contains 3 isozymes: PDHK1, PDHK2 and PDHK4, clear differences in protein expression patterns of the isoforms dependent on developmental stage, overview
Manually annotated by BRENDA team
Rattus norvegicus Fawn-Hooded
-
-
-
Manually annotated by BRENDA team
-
primary, determination of PDK4 expression level in presence or absence of farnesoid X receptor agonists
Manually annotated by BRENDA team
-
PDK2-like isozyme very tightly bound to dihydrolipoyl transacetylase, possibly 2 forms of isozyme PDK2 exist
Manually annotated by BRENDA team
-
isozymes PDK2, PDK3 and PDK4
Manually annotated by BRENDA team
-
green leaf tissue
Manually annotated by BRENDA team
-
a complex signalling mechanism mediates the regulation of the isozymes PDK2 and PDK4 in response to the feeding status of the organism, overview
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK4 are both overexpressed under conditions of starvation, diabetes, or high-fat feeding, low-carbohydrate diet, or due to artificially elevated cAMP or 3,5,3'-triidothyronine levels, reversible by insulin or high-carbohydrate diet
Manually annotated by BRENDA team
-
determination of PDK4 expression level in presence or absence of farnesoid X receptor agonists
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK4
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK4 expression analysis in liver at different developmental stages in diabetic and healthy, starved or fed, rats, overview
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK4, obese Zucker rats show levels of expression of PDK2 and PDK4 in liver and skeletal muscle similar to those found in lean rats
Manually annotated by BRENDA team
Q1KMR4
low expression level of PDK4
Manually annotated by BRENDA team
Mus musculus C75BL/6
-
determination of PDK4 expression level in presence or absence of farnesoid X receptor agonists
-
Manually annotated by BRENDA team
-
isozymes PDK3 and PDK4, low levels of isozyme PDK2
Manually annotated by BRENDA team
-
PDK1 and PDH expression patterns
Manually annotated by BRENDA team
Rattus norvegicus Fawn-Hooded
-
-
-
Manually annotated by BRENDA team
-
lactating, isozyme PDK2
Manually annotated by BRENDA team
-
MCF-7 cells do not express mRNA for pdk4, but express Pdk2
Manually annotated by BRENDA team
-
differentiation of myoblasts to
Manually annotated by BRENDA team
-
primary cortical neurons
Manually annotated by BRENDA team
-
i.e. NSCLC, reduced PDK/PDH activity, PDK1 and PDH expression patterns
Manually annotated by BRENDA team
-
oocyte-specific PDK isoform
Manually annotated by BRENDA team
-
isozyme PDK1-PDK4, with isozymes PDK2 and PDK4 being the most abundant, expression analysis in normal and fasted muscle
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK4
Manually annotated by BRENDA team
-
isozymes PDK2 and PDK4, obese Zucker rats show levels of expression of PDK2 and PDK4 in liver and skeletal muscle similar to those found in lean rats
Manually annotated by BRENDA team
C1IHT9
longissimus dorsal muscle
Manually annotated by BRENDA team
-
extensor digitorum muscle
Manually annotated by BRENDA team
-
isozyme PDK3 with unique E1 subunit probably encoded on the Y-chromosome in contrary to the normal E1 subunit which is encoded on the X-chromosome, regulatory role
Manually annotated by BRENDA team
-
isozyme PDK2, low level
Manually annotated by BRENDA team
additional information
-
isozyme PDK4 is overexpressed in many tissues during diabetes and starvation, particularly important in skeletal and heart muscle
Manually annotated by BRENDA team
additional information
-
selective increase in amount of isozyme PDHK4 protein in both hyperthyroidism and high-fat feeding
Manually annotated by BRENDA team
additional information
-
tissue-specific expression, regulation mechanisms
Manually annotated by BRENDA team
additional information
-
differential tissue-specific expression of isozymes, distribution overview
Manually annotated by BRENDA team
additional information
-
starvation and diabetes mellitus increase PDK4 expression in most tissues, PDK2 especially in liver and kidney
Manually annotated by BRENDA team
additional information
-
tissue-specific induction of PDK4 by statins, fibrates, and anti-bacterial drugs, overview
Manually annotated by BRENDA team
additional information
-
tissue-specific isozyme distribution
Manually annotated by BRENDA team
additional information
Q1KMR4
quantitative PDK4 tissue expression analysis
Manually annotated by BRENDA team
additional information
Q3LTL2
BnPDK1 gene is ubiquitously expressed in almost all the tissues tested, having the highest expression in the stamen and the young silique
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
BCR-ABL, JAK2, and FLT3 are co-localized with PDHK1
Manually annotated by BRENDA team
-
inner membrane matrix compartment
Manually annotated by BRENDA team
-
enzyme contains a 18-amino acid mitochondrial import signal sequence
Manually annotated by BRENDA team
-
purified pyruvate dehydrogenase-complex contains 3 molecules of kinase, but one molecule of dihydrolipoyl transacetylase-protein x-subcomplex of pyruvate dehydrogenase activates more than 15 molecules of kinase
Manually annotated by BRENDA team
-
tightly bound to dihydrolipoamide acetyltransferase of pyruvate dehydrogenase complex
Manually annotated by BRENDA team
-
protein x serves to anchor the kinase to the core of the complex
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
46170
C1IHT9
theoretical
705630
76000
-
recombinant wild-type, gel filtration
642154
80000
-
about, recombinant enzyme, gel filtration
642151
86000
-
approximately, recombinant enzyme with maltose-binding protein cleaved off, gel filtration
642155
90220
-
isozyme PDK2, sedimentation equilibrium centrifugation analysis
662151
92000
Q63065
recombinant hybrid dimer of PDK1 and PDK2, gel filtration; recombinant hybrid dimer of PDK1 and PDK2, gel filtration
642162
100000
-
dimeric enzyme, an intermolecular disulfide between two Cys-392 residues is present, in wild-type enzyme and mutant C45A
722780
100000
-
-
94884
136000
-
pyruvate dehydrogenase, gel filtration
348935
additional information
-
sedimentation equilibrium centrifugation analysis of the pyruvate dehydrogenase complex and components
662151
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 45000, free pyruvate dehydrogenase kinase, SDS-PAGE
?
Q16654
x * 47500, recombinant His-tagged enzyme, SDS-PAGE
?
Q63065
x * 48000, native enzyme, SDS-PAGE, x * 36000, recombinant enzyme, SDS-PAGE
?
-
x * 45066, isozyme PDK2, DNA sequence determination
?
-
x * 45806, recombinant isozyme PDK2, detagged, amino acid determination
?
-
x * 48391, isozyme PDK1, DNA sequence determination, x * 46230, isozyme PDK4, DNA sequence determination
?
-
x * 46504, recombinant isozyme PDK3, detagged, amino acid determination
?
-
x * 45883, isozyme PDK3, DNA sequence determination
?
Q3LTL2
x * 42000, about, sequence calculation
dimer
-
-
dimer
-
homodimer
dimer
-
dimer of monomers built of 2 different domains, crystal structure
dimer
-
1 * 48000, alpha + 1 * 45000, beta, SDS-PAGE
dimer
-
2 * 45000, recombinant wild-type, SDS-PAGE
dimer
-
2 * 43000-43470, mature protein, SDS-PAGE and DNA sequence determination
dimer
-
2 * 44000, recombinant enzyme with maltose-binding protein cleaved off, SDS-PAGE
dimer
-
2 * 45816, sedimentation equilibrium centrifugation analysis in presence of 1% ethylene glycol, 0.1% Pluronics F68, and 0.15 M NaCl
dimer
-
PDHK2 is a component of the pyruvate dehydrogenase complex, complex structure
dimer
-
PDK is a component of the pyruvate dehydrogenase complex bound to the inner lipoyl domains, i.e. L2, of the E2 component, the C-terminus of one PDK subunit constitutes an integral part of the lipoyl-binding pocket in the N-terminus of the opposing other subunit
dimer or tetramer
-
effects of ligand binding on distal structure of PDHK2, analytical ultracentrifugation, structure, overview
homodimer
-
-
additional information
-
subunit composition and complex structure
additional information
-
subunit composition and complex structure
additional information
-
subunit composition and complex structure
additional information
-
kinase activity resides in alpha-subunit
additional information
-
PDK is a component of the pyruvate dehydrogenase complex
additional information
-
PDK is a component of the pyruvate dehydrogenase complex PDC binding the lipoyl domain of E2
additional information
-
PDK is a component of the pyruvate dehydrogenase complex PDC binding the lipoyl domain of E2
additional information
-
PDK is a component of the pyruvate dehydrogenase complex, i.e. PDC, the E2 component of PDC comprises the transacetylase domain, the E1-binding domain, and two lipoyl-bearing domains L1 and L2
additional information
-
a homodimer of pyruvate dehydrogenase kinase is an integral part of the pyruvate dehydrogenase complex, PDC, to which it is anchore primarily through the inner lipoyl-bearing domains L2 of transacetylase component, the PDHK3 subunits have distinct conformations: one subunit exhibits open and the other closed configuration of the putative substrate-binding cleft, domain organization, binding structure, modeling, overview
additional information
-
components and organization of the mammalian pyruvate dehydrogenase complex, including the enzyme
additional information
-
PDHK2 is an integral component of pyruvate dehydrogenase complex tightly bound to the inner lipoyl-bearing domains L2 of the dihydrolipoyl transacetylase component E2 of pyruvate dehydrogenase complex, residues L140, K173, I176, E179 are essential for recognition, and to a lesser extent also D164, D172, and A174, PDHK2 residues forming interfaces with L2, i.e. K17, P22, F31, F44, R372, and K391, are also critical for the maintenance of enhanced PDHK2 activity in the E2-bound state, enzyme structure, overview
additional information
-
pyruvate dehydrogenase complex L2 domain binding structure of isozyme PDK3, overview
additional information
-
structural determinants for cross-talk between PDK3 and lipoyl domain 2 of the pyruvate dehydrogenase complex, overview
additional information
-
the molecular organization of PDH is influenced by Yil042cp, encoding the enzyme, which is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, epitope tagging, overview
additional information
-
structure analysis and comparison,, overview
additional information
-
the molecular organization of PDH is influenced by Yil042cp, encoding the enzyme, which is the kinase of the Saccharomyces cerevisiae pyruvate dehydrogenase complex, epitope tagging, overview
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
tyrosine phosphorylation at Tyr243 of PDHK1 is required for enzyme activity and occurs in human cancers by diverse oncogenic tyrosine kinases, localized to different mitochondrial compartments, tyrosine phosphorylation by FGFR1 enhances PDHK1 activity by promoting ATP and pyruvate dehydrogenase complex binding. FGFR1 activates PDHK1 through direct phosphorylation at multiple tyrosine sites. Phosphorylation at both Y243 and Y244, but not Y136 may be required to promote ATP binding to PDHK1, while Y136 phosphorylation may only function to enhance binding between PDHK1 and pyruvate dehydrogenase complex
phosphoprotein
-
PDK2 performs autophosphorylation in presence of R-lipoic acid
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
phosphorylated and nonphosphorylated components of the pyruvate dehydrogenase complex from heart and kidney
-
isozyme PDHK3 in an asymmetric complex with L2, hanging-drop vapor diffusion technique, mixing of 0.002 ml of protein solution containing 3-5 mg/ml of the PDHK3/L2 complex, 20 mM Tris-HCl, pH 8.0, 100 mM NaCl, 5 mM DTT, and 2.5% v/v ethylene glycol with an equal volume of reservoir solution containing 100 mM histidine, pH 6.4, 30 mM EDTA, and 7% v/v 2,4-methyl penthane diol, X-ray diffraction structure determination and analysis at 2.5 A resolution, molecular replacement, modelling
-
isozyme PDK1 in complex with inhibitors AZD7545 and dichloroacetate, hanging-drop vapor-diffusion method, mixing of 2 ml of PDK1 solution with 50 mg/ml untagged PDK1 in 50 mM potassium phosphate, pH 7.5, 250 mM KCl, 800 mM lysine, 5% glycerol, and 20 mM DTT with 2 ml of well solution containing 0.42 M Na-K-tartrate, 0.1 M Na citrate, pH 5.6,at 20C, 1 week, X-ray diffraction structure determination and analysis at 1.9-2.6 A resolution
-
isozyme PDK4 complexed with either AMPPNP, ADP or inhibitor M77976, screening using the sitting drop vapour diffusion method at 20C, optimized hanging drop vapour diffusion method mixing PDK4 with 10 mM MgCl2, and 5 mM AMPPNP, the reservoir solution contains 1.7 M ammonium sulfate, 2% PEG 400, and Na HEPES, pH 7.1, soaking the PDK4-AMPPNP crystals in 5 mM ADP or 1 mM M77976, X-ray diffraction structure determination and analysis at 1.85-2.53 A resolution, molecular replacement using rat PDK2, PDB entry 1jm6, modeling
Q16654
purified recombinant residues A8-T399 of isozyme PDHK2 free or in complex with ADP and chloroacetate, ATP, Nov3r, Pfz3, or AZ12, hanging drop vapour diffusion method, protein solution contains 10 mg/ml protein, 20 mM Tris-HCl, pH 8.0, 0.15 M NaCl, and 1 mM DTT, versus 0.1 M sodium acetate, pH 5.6-5.8, 6-9% 2-propanol, and 75-125 mM MgCl2, 4C, 2 weeks, complexing with ligands by soaking of PDHK2 crystals in solutions containing 10 mM ATP, 10 mM ADP and 100 mM dichloroacetate, or 1 mM of Nov3r, Pfz3, or AZ12, cryoprotection by 30-35% glycerol, X-ray diffraction structure determination and analysis at 2.2-3.0 A resolution
-
pyruvate dehydrogenase kinase 3 bound to ATP and the lipoyl domain 2 of human pyruvate dehydrogenase complex, X-ray structure determination and analysis at 1.0 A resolution, modeling of closed and open conformation
-
vapor diffusion method, protein 10 mg/ml in 100 mM imidazole or 100 mM MES, pH 6.5-7.0, 0.5 M KCL, 3.5 mM 3-iodopropionic acid, 3.5 mM ADP, 7 mM MgCl2, 6.5% polyethylene glycol 6000, 1.0% ethylene glycol, 1 week, cryoprotection with 25% glycerol, X-ray diffraction structure determination
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
kinase has tendency to aggregate in other buffers than 0.01 M imidazole-asparagine, pH 7.3, 0.1 mM MgCl2, 0.01 M EDTA
-
labile to freeze-thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, 0.02% NaN3, t1/2: 1 month
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant from Escherichia coli as a fusion protein with the maltose-binding protein, to near homogeneity
-
recombinant His6-tagged wild-type and mutant PDKs from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
recombinant from Escherichia coli as His-tagged protein to homogeneity
O02623
2700fold to homogeneity; kidney, from highly purifed pyruvate dehydrogenase-complex
-
kidney, from highly purifed pyruvate dehydrogenase-complex
-
kidney, from highly purifed pyruvate dehydrogenase-complex; removed from the dihydrolipoyl transacetylase by treatment with p-hydroxymercuriphenylsulfonate
-
recombinant wild-type and truncated form from Escherichia coli as His-tagged and maltose-binding fusion protein, respectively, to homogeneity
-
recombinant His-tagged isozymes PDK2 and PDK3 from Escherichia coli BL21(DE3)
-
recombinant His-tagged PDK2, E2, and E3 by nickel affinity chromatography, the His-tag is removable
-
recombinant His-tagged PDK3 from Escherichia coli strain BL21
-
recombinant His-tagged protein from Sf9 insect cells, to near homogeneity
Q16654
recombinant N-terminally His-tagged residues A8-T399 of isozyme PDHK2 from insect cells by nickel affinity chromatography, the His-tag is cleaved off by thrombin
-
with nickel-nitrilotriacetic acid resin and subsequently on a Superdex S200 column
-
free pyruvate dehydrogenase kinase, separable from pyruvate dehydrogenase complex by gel filtration, to homogeneity
-
recombinant from Escherichia coli as His-tagged isozyme PDK1; recombinant His-tagged PDK2 expressed in Escherichia coli; recombinant hybrid dimer of T7-tagged PDK1 and His-tagged PDK2; recombinant hybrid dimer of T7-tagged PDK1 and His-tagged PDK2
Q63065
recombinant from Escherichia coli BL21(DE3) as His-tagged protein, to homogeneity
-
recombinant from Escherichia coli, large scale
Q63065
recombinant His-tagged isozymes PDK1 and PDK2 expressed in Escherichia coli BL21(DE3)
-
recombinant His-tagged isozymes PDK1, PDK2, and PDK4 from Escherichia coli strain BL21
-
recombinant His-tagged PDK2 expressed in Escherichia coli
-
recombinant wild-type and mutants as His-tagged proteins from Escherichia coli BL21(DE3)
Q63065
recombinant c-Myc-tagged or HA-tagged enzyme from strain BY4741 mitochondria by tandem affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
functional expression as maltose-binding protein fusion protein in Escherichia coli
-
PDK DNA sequence determination and analysis, expression of His6-tagged wild-type and mutant PDKs in Escherichia coli strain BL21(DE3)
-
DNA sequence determination and analysis; functional expression in Escherichia coli strain BL21(DE3) as His-tagged protein
-
functional expression in Escherichia coli strain BL21(DE3) as His-tagged protein
-
PDK1, cloned from Brassica cDNA library, DNA and amino acid sequence determination and analysis, BnPDK1 is a multi-copy gene, phylogenetic analysis
Q3LTL2
expression of truncated enzyme forms, comprising residues 284-402 and 1-334, respectively, as maltose-binding-protein fusion proteins in Escherichia coli JM109; functional expression in Escherichia coli as His-tagged protein
-
co-expression of GST-tagged PDHK2 with E1 and E2 components of PDC in Escherichia coli strain BL21(DE3)
-
co-expression of PDK2, E2, and E3 as His-tagged proteins
-
expression analysis and mRNA level determination for isozymes PDK2 and PDK4 in response to several effectors
-
expression in HCT-116 cells
-
expression of GST-tagged PDHK1 in 293T cells, transient co-transfection with wild-type FGFR1 leads to tyrosine phosphorylation of PDHK1, but not in cells co-expressing a kinase dead form of FGFR1. Expression of phosphorylation-deficient, catalytic hypomorph PDHK1 mutants in cancer cells leading to decreased cell proliferation under hypoxia and increased oxidative phosphorylation with enhanced mitochondrial utilization of pyruvate, and expression in xenograft nude mice leads to reduced tumor growth
-
expression of isozyme PDK4 in Escherichia coli, unmodified and modified enzyme
-
expression of isozyme PDK4-luciferase in McA-RH7777 cells using the adenovirus transfection method, PDK2 and PDK4 expression analysis, overview
-
expression of N-terminally His-tagged residues A8-T399 of isozyme PDHK2 in Trichoplusia ni TN5B1-4 insect cells using the baculovirus infection system
-
expression of wild-type and mutant PDHK2 isozymes
-
gene pdk4, DNA and amino sequence determination and analysis, genomic organisation, functional expression of the His-tagged enzyme in Spodoptera frugiperda Sf9 cells via bacuovirus infection system
Q16654
His-tagged PDK3 overexpression in Escherichia coli strain BL21
-
isozymes PDK2 and PDK3, expression in Escherichia coli BL21(DE3) as His-tagged proteins
-
overexpression of isozyme PDK3 in Escherichia coli BL21(DE3) as His-tagged protein
-
overexpression of PDK1 in the rat CNS cell line B12 confers resistance to amyloid-beta peptide and other neurotoxins. Cells expressing PDK1 maintain a lower mitochondrial membrane potential and decreased ROS production with or without exposure to toxins
-
PDK4 gene is located in q21.3 region of chromosome 7, DNA sequence analysis, genomic organization, DNA sequence determination of the partial proximal promotor
-
PDK4, expression of PDK2 and PDK4 in 29T cells, transient expression of PDK4 and PDK4 promoter in CV-1 cells, expression is regulated by retinoic acids and trichostatin A, the proximal promoter contains two retinoic acid response elements binding retinoid X receptor alpha and retinoid acid receptor alpha leading to transcriptional activation, the PDK4 expression activation by all components is prevented by interaction of p300/CBP with E1A, expression analysis, overview
-
wild-type and variant human PDK2 proteins are expressed as N-terminal His6-tagged SUMO fusions
-
4 isozymes: PDK1, PDK2, PDK3, PDK4
-
expressed in Fao cells
-
overexpression of either PDK1 in rat CNS cell line B12 confers resistance to amyloid-beta peptide and other neurotoxins
-
the gene encoding PDK4 is located on chromosome 6, DNA sequence analysis, genomic organization, possible regulatory important elements are Sp1 and CBF sites
-
coexpression of T7-tagged PDK1 and His-tagged PDK2 polypeptides in Escherichia coli, formation of a hybrid dimer; coexpression of T7-tagged PDK1 and His-tagged PDK2 polypeptides in Escherichia coli, formation of a hybrid dimer; expression of isozyme PDK2 as T7-tagged protein in Escherichia coli; expression of isozyme PDK2 in Escherichia coli as His-tagged enzyme; expression of T7-tagged and His-tagged isozyme PDK1 in Escherichia coli
Q63065
DNA and amino acid sequence determination, functional expression as soluble protein in Escherichia coli strain HMS 174 (DE3)
Q63065
DNA sequence determination and analysis of the PDK4 gene promoter, analysis of transcriptional activation mechanism, expression analysis, overview, transient expression of PDK4 promoter mutants in hepatocytes
-
expression of His-tagged isozymes PDK1 and PDK2 in Escherichia coli BL21(DE3)
-
expression of isozyme PDK2 in Escherichia coli as His-tagged enzyme
-
expression of isozyme PDK2 in Escherichia coli as His-tagged protein
-
expression of PDHK2 in HEK293 cells as FLAG-tagged proteins and under a tetracycline-inducible system
-
expression of wild-type and mutant PDHK2s in Escherichia coli
-
expression of wild-type isozyme PDK2 and mutants in Escherichia coli as His-tagged enzymes
Q63065
individual overexpressions of His-tagged isozymes PDK1, PDK2, and PDK4 in Escherichia coli strain BL21
-
isozymes PDK2 and PDK4 expression analysis in liver at different developmental stages
-
overexpression of isozymes PDK1, PDK2, and PDK4 in Escherichia coli BL21(DE3) as His-tagged proteins
-
the gene encoding PDK4 is located on chromosome 4, DNA sequence analysis, genomic organization, possible regulatory important elements are Sp1 and CBF sites
-
isozyme PDK4, DNA and amino acid sequence determination and analysis, expression analysis
Q1KMR4
gene YIL042c, overexpression of c-Myc-tagged or HA-tagged enzyme in strain BY4741
-
a cDNA library is constructed, the pGEM-T and pMD18-T vectors are used
C1IHT9
DNA sequence determination and analysis of different isozymes, phylogenetic analysis, expression analysis of different isozymes
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Pdk2 transcription decreases upon addition of nutlin-3a, nutlin-3a can produce off-target effects, upon reduction of p53, the effect of nutlin-3a upon Pdk2 protein decreases. A histone deacetylase inhibitor, trichostatin A, partially prevents repression of Pdk2 transcription by p53
-
post-mortem brain extracts from patients with Alzheimer disease exhibit a decrease in PDK1 expression compared with nondemented patients
-
cotransfection with plasmids expressing either E2F1 or E2F2 activates Pdk2/luciferase transcription. E2F1 binds less well to the Pdk2 promoter when p53 is induced with zinc
-
FOXO1-mediated 4fold upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
-
HIF-1alpha is a heterodimeric transcription factor that regulates cellular adaptation to hypoxia and induces the transcription of pyruvate dehydrogenase kinase 1
-
the amount of Pdk2 mRNA in both colon and spleen decreases upon irradiation of wild-type mice but not upon irradiation of p53 knockout mice, p53 decreases Pdk2 transcription in vivo
-
Pdk4 gene expression is inhibited by insulin. Knockdown of C/EBPbeta reduces Pdk4 gene expression and decreases the T3 induction of PDK4 in primary hepatocytes
-
C/EBPbeta induces Pdk4 gene expression and increases PDK4 promoter activity, and decreases pyruvate dehydrogenase complex activity. Binding of C/EBPbeta via its sequence elements localized between -634 to -626 and -96 to -87. Pdk4 is also induced by thyroid hormone T3, glucocorticoids, retinoic acid, and long chain fatty acids. The peroxisome proliferator-activated receptor gamma coactivator PGC-1alpha enhances the T3 induction of the Pdk4 expression
-
FOXO1-mediated 4fold upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
-
FOXO1-mediated 4fold upregulation of pyruvate dehydrogenase kinase-4. Pyruvate dehydrogenase kinase is activated in right ventricular hypertrophy, causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores gluccoe oxidation
Rattus norvegicus Fawn-Hooded
-
-
PDK4 activity is increased in most tissues while starvation, exercise and diabetes mellitus
C1IHT9
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E238A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
E238H
-
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
E238Q
-
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
H121A
-
site-directed mutagenesis, 50% decreased trans- and autophosphorylation activity
H121Q
-
site-directed mutagenesis, 50% decreased trans- and autophosphorylation activity
H233A
-
site-directed mutagenesis, reduced activity compared to the wild-type PDK
K241A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type PDK
L234A
-
site-directed mutagenesis, reduced activity compared to the wild-type PDK
D117A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
D164A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
D172A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
D382A/W383A
-
substitutions in the DW-motif
E162A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
E170A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
E179A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
F32A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
F35A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
F48A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
H115A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
I111A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
I157A
-
site-directed mutagenesis, the mutant enzyme shows increased inhibition by dichloroacetate compared to the wild-type PDHK2
I161A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
L140A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is reduced compared to the wild-type isozyme PDK3
L27A
-
site-directed mutagenesis of isozyme PDK3 lipoyl-binding pocket, the mutant has lost its L2 binding and L2-stimulated PDK3 activity
P142A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is unaltered compared to the wild-type isozyme PDK3
R112A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R114A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
R149A
-
substitution of an interacting residue of the DW-motif, mutant shows drastic increase in apparent IC50 value for dichloroacetate, increased affinity for ADP and ATP
R154A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R158A
-
site-directed mutagenesis, the mutant enzyme shows unaltered inhibition by dichloroacetate compared to the wild-type PDHK2
R196A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is slightly reduced compared to the wild-type isozyme PDK3
S83A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
T175A
-
site-directed mutagenesis of isozyme PDK3, the L2 binding is unaltered compared to the wild-type isozyme PDK3
W383F
-
site-directed mutagenesis of isozyme PDHK2, the mutant shows unaltered catalytic activity compared to the wild-type isozyme PDHK2, but altered ligand binding and higher sensitivity to inhibition by pyruvate and ADP
Y145F
-
substitution of an interacting residue of the DW-motif, increased affinity for ADP and ATP
Y145F/R149A
-
mutant shows drastic increase in apparent IC50 value for dichloroacetate
C195A
-
site-directed mutagenesis
C212A
-
site-directed mutagenesis
C395A
-
site-directed mutagenesis
C45A
-
site-directed mutagenesis
D282A
Q63065
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, no activity, not able to bind ATP but the protein substrate
E389A
-
site-directed mutagenesis, the mutant shows unaltered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F168A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F28A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F31A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
F44A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
G284A
Q63065
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, properties similar to wild-type
G286A
Q63065
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, no activity, not able to bind ATP but the protein substrate
G319A
Q63065
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, catalytically active, but very poor binding of ATP
I167A
-
site-directed mutagenesis, the mutant shows slightly altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
K17A
-
site-directed mutagenesis, the mutant shows slightly altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
K368A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
K391A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
L160A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
L23A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
N247A
Q63065
isozyme PDK2, site-directed mutagenesis, mutation of conserved amino acid, no activity, not able to bind ATP but the protein substrate
P22A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
Q47A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
R250A
Q64536
catalytic activity is markedly reduced, Kd value for ATP is 32fold increased, resistant to the inhibitory effect of dichloroacetate, a synthetic analogue of pyruvate
R372A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
T302A
Q64536
catalytic activity is considerably reduced, Kd value for ATP is 24fold increased, resistant to the inhibitory effect of dichloroacetate, a synthetic analogue of pyruvate
Y320F
Q64536
catalytic activity is slightly reduced, Kd value for ATP is decreased to 68%, resistant to the inhibitory effect of dichloroacetate, a synthetic analogue of pyruvate
L234H
-
site-directed mutagenesis, reduced activity compared to the wild-type PDK
additional information
-
construction of transgenic plants with silenced PDHK via expression of an antisense construct driven by both constitutive and seed-specific promoters leading to increased respiration rate in leaves, seed oil content, and seed weight in both cases, mutant phenotypes, overview
additional information
Q3LTL2
overexpression of BnPDK1 in transgenic Arabidopsis thaliana lines repress the pyruvate dehydrogenase complex activity, and results in the decrease of seed oil content and leaf photosynthesis
additional information
-
construction of truncated enzyme forms, the N-terminally truncated form, residues 284-402, is catalytically inactive, the C-terminally reduced form, residues 1-334, shows reduced activity
L53A
-
site-directed mutagenesis, the mutant enzyme shows reduced inhibition by dichloroacetate compared to the wild-type PDHK2
additional information
-
construction of several E2 component-derived domains, overview
additional information
-
overexpression of PDK1 increases the ATP levels and prevents hypoxia-induced reactive oxygen species generation and apoptosis, hypoxia-inducible factor HIF-1 knockout embryonic fibroblasts fail to activate PDK1 and undergo apoptosis with a high rise in reactive oxygen species, hypoxic P493-6 cells with reduced PDK1 levels show impaired growth
additional information
-
serial truncations of the isozyme PDK3 C-terminal tail region either impede or abolish the binding of wild-type L2 to the PDK3 mutants, resulting in the reduction or absence of L2-enhanced kinase activity, overview
additional information
-
RNAi-mediated stable knockdown of endogenous human PDHK1 (hPDHK1) and rescue expression of wild-type and corresponding Y134F and Y239/240F mutant FLAG-tagged mouse PDHK1s to different extents, overview
Y80A
-
site-directed mutagenesis, the mutant enzyme shows no inhibition by dichloroacetate in contrast to the wild-type PDHK2
additional information
-
enzyme-deficient PDHK4-/- mice show lower blood glucose levels and increased pyruvate dehydrogenase complex activity in kidney, gastrocnemius muscle, diaphragm and heart, but not in the liver, compared to the wild-type mice, the mutant mice accumulate less lactate and pyruvate because of a faster rate of pyruvate oxidation and a reduced rate of glycolysis, phenotype, overview, heterozygous mutant mice show about 50% reduced enzyme activity in skeletal muscle, genotype distribution, overview
L45A
-
site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2
additional information
-
construction of PDK4 gene promoter deletion and point mutants for functional analysis, overview
additional information
-
knockdown of C/EBPbeta with siRNA
additional information
-
PDH kinase 1 knockout with siRNA, siRNA transfection into 832/13 clonal beta-cells, transfectant metabolite profiling compared to control cells, overview
additional information
-
stable knockdown of PDK1 in B12 cells by transfection with HuSH 29-mer shRNA
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution of the active pyruvate dehydrogenase complex PDC
-
reconstitution after solubilization with 6 M urea
Q63065
reconstitution of the active pyruvate dehydrogenase complex PDC
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
Q16654
development of specific inhibitors of PDK4 has become an especially important focus for the pharmaceutical management of diabetes and obesity
medicine
-
increased glucose oxidation by inhibition of PDHK activity may be effective for increasing glucose utilization in diabetes treatment
medicine
-
PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders
medicine
-
the results implicate the invariant C-terminal DW-motif anchoring site as a drug target for the inhibition of aberrant PDK activity in cancer and diabetes
pharmacology
-
target for development of specific inhibitors of PDK isozymes to regulate glucose levels in the blood