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Literature summary extracted from

  • Laine, L.M.; Biddau, M.; Byron, O.; Mueller, S.
    Biochemical and structural characterization of the apicoplast dihydrolipoamide dehydrogenase of Plasmodium falciparum (2015), Biosci. Rep., 35, e00171.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.8.1.4 drug development a homology model for PfaE3 reveals an extra anti-parallel beta-strand at the position where human E3BP (E3-binding protein) interacts with E3, a parasite-specific feature that may be exploitable for drug discovery against pyruvate dehydrogenase complex, PDC. Plasmodium PDC is essential for parasite survival in the mosquito vector and for late liver stage development in the human host, suggesting its suitability as a target for intervention strategies against malaria Plasmodium falciparum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.8.1.4 gene Pfae3, recombinant expression of His-tagged enzyme in Escherichia coli strain NovaBlue (DE3), transfection of pCC1-Pfae3 Plasmodium falciparum 3D7 erythrocytic stages Plasmodium falciparum

Protein Variants

EC Number Protein Variants Comment Organism
1.8.1.4 additional information generation of Pfae3 deletion mutants of Plasmodium falciparum, the gene is replaced by the selectable marker hdhfr after initial positive selection with WR99210 followed by negative selection using 5-fluorocytosine generating the line 3D7DELTAae3, phenotype, overview Plasmodium falciparum

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.8.1.4 0.015
-
NADH pH 7.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum
1.8.1.4 0.096
-
NAD+ pH 8.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum
1.8.1.4 0.841
-
Lipoamide pH 7.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum
1.8.1.4 1.16
-
dihydrolipoamide pH 8.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.8.1.4 apicoplast in the human malaria parasite Plasmodium falciparum, the single PDC enzyme complex with enzyme E3 is located exclusively in the apicoplast Plasmodium falciparum 20011
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.8.1.4 127478
-
sequence calculation Plasmodium falciparum
1.8.1.4 128000 140000 gel filtration and analytical ultracentrifugation Plasmodium falciparum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.8.1.4 dihydrolipoamide + NAD+ Plasmodium falciparum
-
lipoamide + NADH + H+
-
r
1.8.1.4 lipoamide + NADH + H+ Plasmodium falciparum
-
dihydrolipoamide + NAD+
-
r

Organism

EC Number Organism UniProt Comment Textmining
1.8.1.4 Plasmodium falciparum
-
-
-
3.1.22.1 Caenorhabditis elegans Q17778
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.8.1.4 recombinant His-tagged enzyme from Escherichia coli strain NovaBlue (DE3) by nickel affinity chromatography and gel filtration Plasmodium falciparum

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.1.22.1 embryo
-
Caenorhabditis elegans
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.8.1.4 dihydrolipoamide + NAD+
-
Plasmodium falciparum lipoamide + NADH + H+
-
r
1.8.1.4 lipoamide + NADH + H+
-
Plasmodium falciparum dihydrolipoamide + NAD+
-
r
3.1.22.1 DNA + H2O method of ToLFP (topoisomerase ligation fluorescence probes) is used for directly visualizing DNA fragments generated by DNase II in Caenorhabditis elegans embryos. The ratio of non-autonomous and autonomous modes of DNase II is about 3-7. ToLFP method can be used to differentiate the locations of blastomeres where DNase II acts autonomously or non-autonomously in degrading apoptotic DNA Caenorhabditis elegans ?
-
?

Subunits

EC Number Subunits Comment Organism
1.8.1.4 homodimer 2 * 64000, recombinant Hs-tagged enzyme, SDS-PAGE Plasmodium falciparum
1.8.1.4 More E3 enzyme homology structure modelling using the human enzyme structure, PDB ID 2F5Z Plasmodium falciparum

Synonyms

EC Number Synonyms Comment Organism
1.8.1.4 apicoplast E3
-
Plasmodium falciparum
1.8.1.4 dihydrolipoamide dehydrogenase
-
Plasmodium falciparum
1.8.1.4 E3
-
Plasmodium falciparum
1.8.1.4 PfaE3
-
Plasmodium falciparum
3.1.22.1 DNase II
-
Caenorhabditis elegans

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.8.1.4 25
-
assay at Plasmodium falciparum

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.8.1.4 77.8
-
NADH pH 7.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum
1.8.1.4 97
-
Lipoamide pH 7.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum
1.8.1.4 110
-
NAD+ pH 8.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum
1.8.1.4 110
-
dihydrolipoamide pH 8.0, 25°C, recombinant His-tagged enzyme Plasmodium falciparum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.8.1.4 7
-
assay at, reduction of lipoamide with NADH Plasmodium falciparum
1.8.1.4 8
-
assay at, oxidation of dihydrolipoamide with NAD+ Plasmodium falciparum

Cofactor

EC Number Cofactor Comment Organism Structure
1.8.1.4 NAD+
-
Plasmodium falciparum
1.8.1.4 NADH
-
Plasmodium falciparum

General Information

EC Number General Information Comment Organism
1.8.1.4 malfunction Pfae3 is deleted from Plasmodium falciparum and although the mutants are viable, they display a highly synchronous growth phenotype during intra-erythrocytic development. The mutants also show changes in the expression of some mitochondrial and antioxidant proteins suggesting that deletion of Pfae3 impacts on the parasite's metabolic function with downstream effects on the parasite's redox homoeostasis and cell cycle Plasmodium falciparum
1.8.1.4 additional information a homology model for PfaE3 reveals an extra anti-parallel beta-strand at the position where human E3BP (E3-binding protein) interacts with E3, a parasite-specific feature that may be exploitable for drug discovery against PDC. E3 enzyme homology structure modelling using the human enzyme structure, PDB ID 2F5Z Plasmodium falciparum
1.8.1.4 physiological function pyruvate dehydrogenase complex, PDC, is a multi-enzyme complex comprising an E1, pyruvate decarboxylase, an E2, dihydrolipomide acetyltransferase, and an E3, dihydrolipoamide dehydrogenase. Plasmodium PDC is essential for parasite survival in the mosquito vector and for late liver stage development in the human host Plasmodium falciparum
3.1.22.1 physiological function NUC-1 is the major DNase II for degrading apoptotic DNA Caenorhabditis elegans