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Literature summary for 1.1.1.41 extracted from

  • Bzymek, K.P.; Colman, R.F.
    Role of alpha-Asp181, beta-Asp192, and gamma-Asp190 in the distinctive subunits of human NAD-specific isocitrate dehydrogenase (2007), Biochemistry, 46, 5391-5397.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
ADP activates. Michaelis-Menten constant for DL-isocitrate is lowered 3.5-fold in the wild-type IDH. The substitution of asparagine for aspartate in alpha-mutant enzyme D181N, beta-subunit mutant enzyme D192N, and gamma-subunit mutant enzyme D190N abolishes this allosteric effect of ADP on Km Homo sapiens

Protein Variants

Protein Variants Comment Organism
D181N mutation in the alpha-subunit exhibits a 2000fold decrease in Vmax, with increases of 15fold in the Kms for Mn2+ and NAD+ and a much smaller change in the Km for isocitrate. Mutant enzyme fails to respond to ADP by lowering the Km for isocitrate, although it binds to ADP Homo sapiens
D190N mutation in the gamma-subunit results in 4-5fold decrease in Vmax as compared to wild-type enzyme. The Km-values for NAD+ and for Mn2+ of the mutant enzyme are 19 and 72 times, respectively, that of the wild-type enzyme with a much smaller effect on the Km for isocitrate. Mutant enzyme fails to respond to ADP by lowering the Km for isocitrate, although it binds to ADP Homo sapiens
D192N mutation in the beta-subunit results in 4-5fold decrease in Vmax as compared to wild-type enzyme. The Km-value for NAD+ of the mutant enzyme is 9times that of the normal enzyme with little or no effect on the affinity for Mn2+ or isocitrate. Mutant enzyme fails to respond to ADP by lowering the Km for isocitrate, although it binds to ADP Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.08
-
NAD+ pH 7.2, wild-type enzyme Homo sapiens
0.71
-
NAD+ pH 7.2, beta-subunit mutant enzyme D192N Homo sapiens
1.2
-
NAD+ pH 7.2, alpha-subunit mutant enzyme D181N Homo sapiens
1.5
-
NAD+ pH 7.2, gamma-subunit mutant enzyme D190N Homo sapiens
2.4
-
isocitrate pH 7.2, wild-type enzyme Homo sapiens
2.9
-
isocitrate pH 7.2, beta-subunit mutant enzyme D192N Homo sapiens
9.1
-
isocitrate pH 7.2, alpha-subunit mutant enzyme D181N Homo sapiens
13
-
isocitrate pH 7.2, gamma-subunit mutant enzyme D190N Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mn2+ required. KM-value: 0.067 mM for wild-type enzyme, 1.09 mM for the alpha-subunit mutant D181N, 0.14 mM for the beta-subunit mutant D192N. 4.8 mM for the gamma-subunit mutant D190N Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
238000
-
gel filtration Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
isocitrate + NAD+
-
Homo sapiens 2-oxoglutarate + CO2 + NADH + H+
-
?

Subunits

Subunits Comment Organism
More the ratios of the alpha-, beta-, and gamma-subunits of the wild-type and three mutant enzymes all approximate 2:1:1 Homo sapiens

Synonyms

Synonyms Comment Organism
NAD-specific isocitrate dehydrogenase
-
Homo sapiens