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Literature summary for 1.1.1.42 extracted from

  • Dang, L.; White, D.W.; Gross, S.; Bennett, B.D.; Bittinger, M.A.; Driggers, E.M.; Fantin, V.R.; Jang, H.G.; Jin, S.; Keenan, M.C.; Marks, K.M.; Prins, R.M.; Ward, P.S.; Yen, K.E.; Liau, L.M.; Rabinowitz, J.D.; Cantley, L.C.; Thompson, C.B.; Vander Heiden, M.G.; Su, S.M.
    Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (2009), Nature, 462, 739-744.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.1.1.42

Cloned(Commentary)

Cloned (Comment) Organism
expression of myc-tagged wild-type IDH1 and R132H mutant IDH1 in U-87MG glioblastoma cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
R132H naturally occuring mutant of IDH1, the mutation causes loss in binding affinity for both isocitrate and MgCl2 along with a 1000fold decrease in catalytic turnover. The mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1, metabolite profiling in comparison to the wild-type IDH1, overview. Mutation to histidine results in a significant shift in position of the highly conserved residues Y139 from the A subunit and K212' from the B subunit both of which are thought to be critical for catalysis by this enzyme family. exchange of Arg132 to His affects the conformation equilibrium and the reorganization of the active-site. Also, not only the expected loss of key salt-bridge interactions between the guanidinium of R132 and the alpha/beta carboxylates of isocitrate, as well as changes in the network that coordinates the metal ion, but also an unexpected reorganization of the active-site, structure analyis, overview Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol isozyme IDH1 Homo sapiens 5829
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ activates Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
isocitrate + NADP+ Homo sapiens
-
 2-oxoglutarate + NADPH + H+ + CO2
-
 ?
additional information Homo sapiens the R132H mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1 ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens O75874
-
-

Source Tissue

Source Tissue Comment Organism Textmining
glioblastoma cell of secondary glioblastomas Homo sapiens
-
glioma cell of grade II-III gliomas Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
isocitrate + NADP+
-
 Homo sapiens 2-oxoglutarate + NADPH + H+ + CO2
-
 ?
additional information the R132H mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1 Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
More exchange of Arg132 to His affects the conformation equilibrium and the reorganization of the active-site. Also, not only the expected loss of key salt-bridge interactions between the guanidinium of R132 and the alpha/beta carboxylates of isocitrate, as well as changes in the network that coordinates the metal ion, but also an unexpected reorganization of the active-site, structure analyis, overview Homo sapiens

Synonyms

Synonyms Comment Organism
cytosolic isocitrate dehydrogenase 1
-
 Homo sapiens
IDH1
-
 Homo sapiens
isocitrate dehydrogenase 1
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADP+
-
 Homo sapiens

General Information

General Information Comment Organism
metabolism metabolite profiling identifies elevated 2-hydroxyglutarate levels in IDH1 mutant R132H expressing cells compared to wild-type Homo sapiens
additional information mutations in the enzyme cytosolic IDH1 at R132 are a common feature of a major subset of primary human brain cancers, especially in grade II-III gliomas and secondary glioblastomas. The mutations result in loss of the enzyme's ability to catalyze conversion of isocitrate to 2-oxoglutarate. Expression of R132H mutant IDH1 results in no measurable production of NADPH from isocitrate, and isocitrate-dependent NADPH production increases with increasing amounts of wild-type enzyme Homo sapiens