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Literature summary for 1.1.1.42 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

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

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

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required for catalysis 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 + CO2 + NADPH + H+
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Reaction

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 and Products (Substrate)

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

Subunits

Subunits Comment Organism
homodimer
-
Homo sapiens

Synonyms

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

Cofactor

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

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