Application | Comment | Organism |
---|---|---|
additional information | future clinical and bioengineering applications of hICDH can be in the development of techniques to regulate the growth of glioblastomas and to capture and store carbon dioxide | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required for catalysis | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
isocitrate + NADP+ | Homo sapiens | - |
2-oxoglutarate + CO2 + NADPH + H+ | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+ | overall reaction, catalytic mechanism, overview. The catalysis proceeds in three steps: (1) NADP+ reduction by the isocitrate substrate with the help of the Lys212B base, (2) beta-decarboxylation of the resulting oxalosuccinate, generating an enolate, and (3) protonation of this intermediate by Tyr139A, giving rise to the 2-oxooglutarate product. The beta-decarboxylation of oxalosuccinate is the most likely rate-limiting step. Role of Mg2+ and Asp275A, whose acid/base properties throughout the catalytic cycle lower the barrier to physiologically competent values. The catalysis takes place in a closed-conformation quaternary complex and involves significant conformational changes as the divalent metal (Mg2+ or Mn2+), the NADP+ cofactor, and the trianionic form of the isocitrate substrate (ICT) sequentially bind | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
isocitrate + NADP+ | - |
Homo sapiens | 2-oxoglutarate + CO2 + NADPH + H+ | - |
r |
Subunits | Comment | Organism |
---|---|---|
homodimer | - |
Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
HICDH | - |
Homo sapiens |
NADP+-dependent isocitrate dehydrogenase | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | NADP+ is anchored in the active site by a tetrad composed of Lys72A, Thr75A, Asn96A, and Glu306A | Homo sapiens | |
NADPH | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
additional information | molecular enzyme structure and active site modelling, QM/MM calculations, and structure-function analysis, detailed overview | Homo sapiens |
physiological function | the cytosolic homodimeric isocitrate dehydrogenase (hICDH) is involved in the regulation of tumorogenesis | Homo sapiens |