Literature summary for 2.7.11.2 extracted from

Li, J.; Kato, M.; Chuang, D.T.
Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate (2009), J. Biol. Chem., 284, 34458-34467.

Search for more literature for 2.7.11.2

Application

Application	Comment	Organism
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	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
wild-type and variant human PDK2 proteins are expressed as N-terminal His6-tagged SUMO fusions	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
D382A/W383A	substitutions in the DW-motif	Homo sapiens
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	Homo sapiens
Y145F	substitution of an interacting residue of the DW-motif, increased affinity for ADP and ATP	Homo sapiens
Y145F/R149A	mutant shows drastic increase in apparent IC50 value for dichloroacetate	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
Dichloroacetate	-	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + [pyruvate dehydrogenase (acetyl-transferring)]	Homo sapiens	-	ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
with nickel-nitrilotriacetic acid resin and subsequently on a Superdex S200 column	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + [pyruvate dehydrogenase (acetyl-transferring)]	-	Homo sapiens	ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate	-	?

Subunits

Subunits	Comment	Organism
homodimer	-	Homo sapiens

Synonyms

Synonyms	Comment	Organism
PDK2	-	Homo sapiens
pyruvate dehydrogenase kinase 2	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
23	-	activity assay	Homo sapiens

pH Optimum

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

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.29	-	wild-type enzyme, apparent IC50 for basal activity	Homo sapiens	Dichloroacetate
0.48	-	wild-type enzyme, apparent IC50 for E2p/E3BP-dependent activity	Homo sapiens	Dichloroacetate
3.04	-	mutant Y145F, apparent IC50 for basal activity	Homo sapiens	Dichloroacetate
3.24	-	mutant Y145F, apparent IC50 for E2p/E3BP-dependent activity	Homo sapiens	Dichloroacetate
35.3	-	mutant D382A/W383A, apparent IC50 for E2p/E3BP-dependent activity	Homo sapiens	Dichloroacetate
37.9	-	mutant D382A/W383A, apparent IC50 for basal activity	Homo sapiens	Dichloroacetate
86.3	-	mutant Y145F/R149A, apparent IC50 for E2p/E3BP-dependent activity	Homo sapiens	Dichloroacetate
98.7	-	mutant R149A, apparent IC50 for basal activity	Homo sapiens	Dichloroacetate
102	-	mutant Y145F/R149A, apparent IC50 for basal activity	Homo sapiens	Dichloroacetate
108	-	mutant R149A, apparent IC50 for E2p/E3BP-dependent activity	Homo sapiens	Dichloroacetate

General Information

General Information	Comment	Organism
physiological function	the mitochondrial pyruvate dehydrogenase complex, PDC, is down-regulated by phosphorylation catalyzed by pyruvate dehydrogenase kinase isoforms	Homo sapiens

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Release 2023.1 (January 2023)