Application | Comment | Organism |
---|---|---|
medicine | PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of N-terminally His-tagged residues A8-T399 of isozyme PDHK2 in Trichoplusia ni TN5B1-4 insect cells using the baculovirus infection system | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
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, 4°C, 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 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
ADP | binding site structure, involves Gly319 and Phe318, and K+ ions | Homo sapiens | |
AZ12 | i.e. N-[4-([ethylanilino]sulfonyl)2-methylphenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, binding structure, requires K+ for inhibition | Homo sapiens | |
Dichloroacetate | binds at the pyruvate binding site, binding structure, involves e.g. Arg154 | Homo sapiens | |
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 | Homo sapiens | |
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 | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrion | - |
Homo sapiens | 5739 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
K+ | binds via Gly319, involved in inhibition by ADP, Nov3r, and AZ12, and in binding of ATP | Homo sapiens | |
Mg2+ | - |
Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + pyruvate dehydrogenase | Homo sapiens | 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 | ADP + phosphorylated pyruvate dehydrogenase | - |
? | |
additional information | Homo sapiens | PDK regulates the pyruvate dehydrogenase multienzyme complex activity | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
isozyme PDHK2; isozyme PDHK2 | - |
Purification (Comment) | Organism |
---|---|
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 | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + pyruvate dehydrogenase | - |
Homo sapiens | ADP + phosphorylated pyruvate dehydrogenase | - |
? | |
ATP + pyruvate dehydrogenase | 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 | Homo sapiens | ADP + phosphorylated pyruvate dehydrogenase | - |
? | |
additional information | PDK regulates the pyruvate dehydrogenase multienzyme complex activity | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | PDHK2 is a component of the pyruvate dehydrogenase complex, complex structure | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
PDHK2 | - |
Homo sapiens |
pyruvate dehydrogenase kinase 2 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | binding site structure, involves Gly317 and Tyr320, and K+ ions | Homo sapiens |