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Literature summary extracted from

  • Neves, R.; Fernandes, P.; Ramos, M.
    Unveiling the catalytic mechanism of NADP+-dependent isocitrate dehydrogenase with QM/MM calculations (2016), ACS Catal., 6, 357-368.
No PubMed abstract available

Application

EC Number Application Comment Organism
1.1.1.42 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

EC Number Localization Comment Organism GeneOntology No. Textmining
1.1.1.42 cytosol
-
 Homo sapiens 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.1.1.42 Mg2+ required for catalysis Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.42 isocitrate + NADP+ Homo sapiens
-
 2-oxoglutarate + CO2 + NADPH + H+
-
 r

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.42 Homo sapiens
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.1.1.42 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
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.42 isocitrate + NADP+
-
 Homo sapiens 2-oxoglutarate + CO2 + NADPH + H+
-
 r

Subunits

EC Number Subunits Comment Organism
1.1.1.42 homodimer
-
 Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.1.1.42 HICDH
-
 Homo sapiens
1.1.1.42 NADP+-dependent isocitrate dehydrogenase
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.42 NADP+ NADP+ is anchored in the active site by a tetrad composed of Lys72A, Thr75A, Asn96A, and Glu306A Homo sapiens
1.1.1.42 NADPH
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.1.1.42 additional information molecular enzyme structure and active site modelling, QM/MM calculations, and structure-function analysis, detailed overview Homo sapiens
1.1.1.42 physiological function the cytosolic homodimeric isocitrate dehydrogenase (hICDH) is involved in the regulation of tumorogenesis Homo sapiens