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Literature summary for 2.7.11.5 extracted from

  • Zheng, J.; Jia, Z.
    Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase (2010), Nature, 465, 961-965.
    View publication on PubMed
Search for more literature for 2.7.11.5

Protein Variants

Protein Variants Comment Organism
D475A site-directed mutagenesis, the mutant shows completely reduced activity compared to the wild-type enzyme Escherichia coli
D477A site-directed mutagenesis, the mutant shows only slightly reduced activity compared to the wild-type enzyme Escherichia coli
E478A site-directed mutagenesis, the mutant shows slightly increased activity compared to the wild-type enzyme Escherichia coli
E497K/E499K site-directed mutagenesis, the mutant shows about 75% reduced activity compared to the wild-type enzyme Escherichia coli
K291A site-directed mutagenesis, the mutant shows unaltered activity compared to the wild-type enzyme Escherichia coli
K336A site-directed mutagenesis, the mutant shows completely reduced activity compared to the wild-type enzyme Escherichia coli
K346E site-directed mutagenesis, the mutant shows only slightly reduced activity compared to the wild-type enzyme Escherichia coli
N462A site-directed mutagenesis, the mutant shows about 75% reduced activity compared to the wild-type enzyme Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
AMP acts as an AceK phosphatase activator and kinase inhibitor, AMP binds in an allosteric site between the two AceK domains, allosteric AMP-binding site, structure modeling, overview Escherichia coli

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
65000
-
-
 Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [isocitrate dehydrogenase (NADP+)] Escherichia coli
-
 ADP + [isocitrate dehydrogenase (NADP+)] phosphate
-
 r
ATP + [isocitrate dehydrogenase (NADP+)] Escherichia coli 0157:H7
-
 ADP + [isocitrate dehydrogenase (NADP+)] phosphate
-
 r

Organism

Organism UniProt Comment Textmining
Escherichia coli Q8X607
-
-
Escherichia coli 0157:H7 Q8X607
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [isocitrate dehydrogenase (NADP+)]
-
 Escherichia coli ADP + [isocitrate dehydrogenase (NADP+)] phosphate
-
 r
ATP + [isocitrate dehydrogenase (NADP+)] The substrate recognition loop of AceK binds to the ICDH dimer, allowing higher order substrate recognition and interaction, and inducing critical conformational change at the phosphorylation site of ICDH Escherichia coli ADP + [isocitrate dehydrogenase (NADP+)] phosphate
-
 r
ATP + [isocitrate dehydrogenase (NADP+)]
-
 Escherichia coli 0157:H7 ADP + [isocitrate dehydrogenase (NADP+)] phosphate
-
 r
ATP + [isocitrate dehydrogenase (NADP+)] The substrate recognition loop of AceK binds to the ICDH dimer, allowing higher order substrate recognition and interaction, and inducing critical conformational change at the phosphorylation site of ICDH Escherichia coli 0157:H7 ADP + [isocitrate dehydrogenase (NADP+)] phosphate
-
 r
additional information bifunctional AceK possesses the two opposing activities of protein kinase and phosphatase within one protein, and specifically recognizes only intact ICDH. Additionally, AceK has strong ATPase activity Escherichia coli ?
-
 ?
additional information bifunctional AceK possesses the two opposing activities of protein kinase and phosphatase within one protein, and specifically recognizes only intact ICDH. Additionally, AceK has strong ATPase activity Escherichia coli 0157:H7 ?
-
 ?

Subunits

Subunits Comment Organism
More architecture of the AceK structure as both a kinase domain and a regulatory domain. The domains exist as an inactive protein complex of a catalytic subunit and a regulatory subunit. Although the regulatory subunit is a separate protein, its binding of ligands facilitates activation of the catalytic subunit Escherichia coli

Synonyms

Synonyms Comment Organism
AceK
-
 Escherichia coli
bifunctional isocitrate dehydrogenase kinase/phosphatase
-
 Escherichia coli

Cofactor

Cofactor Comment Organism Structure
ATP ATP-binding site, structure modeling, overview Escherichia coli

General Information

General Information Comment Organism
evolution AceK is significantly larger than typical eukaryotic protein kinases. Apart from the ATP-binding motif, AceK does not share sequence homology with any eukaryotic protein kinase or phosphatase Escherichia coli
metabolism Escherichia coli isocitrate dehydrogenase kinase/phosphatase is a unique bifunctional enzyme that phosphorylates or dephosphorylates isocitrate dehydrogenase, ICDH, in response to environmental changes, resulting in the inactivation or, respectively, activation of ICDH1. ICDH inactivation short-circuits the Krebs cycle by enabling the glyoxlate bypass Escherichia coli
additional information structures of AceK and its complex with ICDH. AceK contains a eukaryotic protein-kinase-like domain containing ATP and a regulatory domain with a distinct fold. AMP-mediated conformational change exposes and shields ATP, acting as a switch between AceK kinase and phosphatase activities, and ICDH-binding induces further conformational change for AceK activation. The substrate recognition loop of AceK binds to the ICDH dimer, allowing higher order substrate recognition and interaction, and inducing critical conformational change at the phosphorylation site of ICDH, structure-based recognition of Asp 477 being located at the ATP-binding site Escherichia coli