Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | E2-dependent PDHK2 activation, molecular modeling and mechanism | Rattus norvegicus |
Cloned (Comment) | Organism |
---|---|
expression of wild-type and mutant PDHK2s in Escherichia coli | Rattus norvegicus |
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 | 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 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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrion | - |
Rattus norvegicus | 5739 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Rattus norvegicus |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | - |
- |
- |
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 | 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 | Comment | Organism |
---|---|---|
PDHK2 | - |
Rattus norvegicus |
pyruvate dehydrogenase kinase 2 | - |
Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.8 | - |
assay at | Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Rattus norvegicus |