BRENDA - Enzyme Database

Unveiling the catalytic mechanism of NADP+-dependent isocitrate dehydrogenase with QM/MM calculations

Neves, R.; Fernandes, P.; Ramos, M.; ACS Catal. 6, 357-368 (2016)
No PubMed abstract available

Data extracted from this reference:

Application
EC Number
Application
Commentary
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
Commentary
Organism
GeneOntology No.
Textmining
1.1.1.42
cytosol
-
Homo sapiens
5829
-
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
1.1.1.42
Mg2+
required for catalysis
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.1.42
isocitrate + NADP+
Homo sapiens
-
2-oxoglutarate + CO2 + NADPH + H+
-
-
r
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.1.1.42
Homo sapiens
-
-
-
Reaction
EC Number
Reaction
Commentary
Organism
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
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.42
isocitrate + NADP+
-
739770
Homo sapiens
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
Subunits
EC Number
Subunits
Commentary
Organism
1.1.1.42
homodimer
-
Homo sapiens
Cofactor
EC Number
Cofactor
Commentary
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
Application (protein specific)
EC Number
Application
Commentary
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
Cofactor (protein specific)
EC Number
Cofactor
Commentary
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
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
1.1.1.42
cytosol
-
Homo sapiens
5829
-
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
1.1.1.42
Mg2+
required for catalysis
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.1.42
isocitrate + NADP+
Homo sapiens
-
2-oxoglutarate + CO2 + NADPH + H+
-
-
r
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.42
isocitrate + NADP+
-
739770
Homo sapiens
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
1.1.1.42
homodimer
-
Homo sapiens
General Information
EC Number
General Information
Commentary
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
General Information (protein specific)
EC Number
General Information
Commentary
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