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Literature summary for 2.7.11.2 extracted from

  • Tuganova, A.; Klyuyeva, A.; Popov, K.M.
    Recognition of the inner lipoyl-bearing domain of dihydrolipoyl transacetylase and of the blood glucose-lowering compound AZD7545 by pyruvate dehydrogenase kinase 2 (2007), Biochemistry, 46, 8592-8602.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
additional information E2-dependent PDHK2 activation, molecular modeling and mechanism Rattus norvegicus

Cloned(Commentary)

Cloned (Comment) Organism
expression of wild-type and mutant PDHK2s in Escherichia coli Rattus norvegicus

Protein Variants

Protein Variants Comment Organism
E389A site-directed mutagenesis, the mutant shows unaltered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
F168A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
F28A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
F31A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
F44A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
I167A site-directed mutagenesis, the mutant shows slightly altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
K17A site-directed mutagenesis, the mutant shows slightly altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
K368A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
K391A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
L160A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
L23A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
L45A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
P22A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
Q47A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus
R372A site-directed mutagenesis, the mutant shows altered L2 component binding within the pyruvate dehydrogenase complex compared to the wild-type PDHK2 Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
AZD7545 compound AZD7545 disrupts the interactions between PDHK2 and L2 and thereby inhibits PDHK2 activity Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information binding of wild-type and mutant PDHK2 proteins to the unaltered L2 domain, kinetics Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Rattus norvegicus 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + pyruvate dehydrogenase complex Rattus norvegicus
-
ADP + phosphorylated pyruvate dehydrogenase complex
-
?

Organism

Organism UniProt Comment Textmining
Rattus norvegicus
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + pyruvate dehydrogenase complex
-
Rattus norvegicus ADP + phosphorylated pyruvate dehydrogenase complex
-
?
ATP + pyruvate dehydrogenase complex 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 Rattus norvegicus ADP + phosphorylated pyruvate dehydrogenase complex
-
?
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 Rattus norvegicus ?
-
?

Subunits

Subunits Comment Organism
More 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 Rattus norvegicus

Synonyms

Synonyms Comment Organism
PDHK2
-
Rattus norvegicus
pyruvate dehydrogenase kinase 2
-
Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.8
-
assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
ATP
-
Rattus norvegicus