Literature summary for 2.7.11.2 extracted from

Kato, M.; Li, J.; Chuang, J.L.; Chuang, D.T.
Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol (2007), Structure, 15, 992-1004.

Activating Compound

Activating Compound	Comment	Organism	Structure
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	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
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 20°C, 1 week, X-ray diffraction structure determination and analysis at 1.9-2.6 A resolution	Homo sapiens

Crystallization (Comment)

Organism

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 20°C, 1 week, X-ray diffraction structure determination and analysis at 1.9-2.6 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
ADP	synergism with dichloroacetate	Homo sapiens
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	Homo sapiens
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	Homo sapiens
radicicol	binding site structure, structural mechanisms for inhibition of pyruvate dehydrogenase kinase isozymes, binding structure analysis, overview	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Homo sapiens	5739	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	-	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	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	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q15118	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	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	Homo sapiens	?	-	?
additional information	ligand binding by isozyme PDK1 involves the conserved Ser75	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
More	pyruvate dehydrogenase complex L2 domain binding structure of isozyme PDK3, overview	Homo sapiens

Synonyms

Synonyms	Comment	Organism
PDK	-	Homo sapiens
pyruvate dehydrogenase kinase	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.087	-	pH 7.5, 25°C, inhibition of isozyme PDK1	Homo sapiens	AZD7545
0.23	-	pH 7.5, 25°C, inhibition of isozyme PDK1	Homo sapiens	radicicol
0.4	-	pH 7.5, 25°C, inhibition of isozyme PDK3	Homo sapiens	radicicol
0.6	-	pH 7.5, 25°C, inhibition of isozyme PDK3	Homo sapiens	AZD7545