Cloned (Comment) | Organism |
---|---|
expression of myc-tagged wild-type IDH1 and R132H mutant IDH1 in U-87MG glioblastoma cells | Homo sapiens |
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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | isozyme IDH1 | Homo sapiens | 5829 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | activates | Homo sapiens |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O75874 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
glioblastoma cell | of secondary glioblastomas | Homo sapiens | - |
glioma cell | of grade II-III gliomas | Homo sapiens | - |
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 | 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 | Comment | Organism |
---|---|---|
cytosolic isocitrate dehydrogenase 1 | - |
Homo sapiens |
IDH1 | - |
Homo sapiens |
isocitrate dehydrogenase 1 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Homo sapiens |
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 |