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Literature summary for 2.5.1.92 extracted from

  • Jordao, F.M.; Gabriel, H.B.; Alves, J.M.; Angeli, C.B.; Bifano, T.D.; Breda, A.; de Azevedo, M.F.; Basso, L.A.; Wunderlich, G.; Kimura, E.A.; Katzin, A.M.
    Cloning and characterization of bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase from Plasmodium falciparum (2013), Malar. J., 12, 184.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the enzyme possibly represents an attractive drug target for the development of selective inhibitors aiming the erythrocytic stages of Plasmodium falciparum and development of more potent bisphosphonate-based inhibitors selectivity targeting this key point of the plasmodial isoprenoid metabolism Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment) Organism
gene PF3D7_1128400, DNA and amino acid sequence determination and analysis, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21(DE3+) pLys RIL Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
additional information the enzyme is inhibited by nitrogen-containing bisphosphonates Plasmodium falciparum
risedronate competitive inhibitor Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten kinetics Plasmodium falciparum
0.002
-
isopentenyl diphosphate pH 7.5, 37°C, recombinant enzyme, with dimethylallyl diphosphate Plasmodium falciparum
0.068
-
dimethylallyl diphosphate pH 7.5, 37°C, recombinant enzyme, with isopentenyl diphosphate Plasmodium falciparum

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Plasmodium falciparum

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
70000
-
-
Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
dimethylallyl diphosphate + 2 isopentenyl diphosphate Plasmodium falciparum
-
2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate Plasmodium falciparum clone 3D7
-
2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
?
additional information Plasmodium falciparum a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum ?
-
?
additional information Plasmodium falciparum clone 3D7 a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum ?
-
?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum
-
gene PF3D7_1128400
-
Plasmodium falciparum clone 3D7
-
gene PF3D7_1128400
-

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3+) pLys RIL by glutathione affinity chromatography to homogeneity Plasmodium falciparum

Source Tissue

Source Tissue Comment Organism Textmining
additional information the enzyme is constitutively expressed in all stages during the asexual intra-erythrocytic cycle of Plasmodium falciparum, overview Plasmodium falciparum
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dimethylallyl diphosphate + 2 isopentenyl diphosphate
-
Plasmodium falciparum 2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
-
Plasmodium falciparum clone 3D7 2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
?
additional information a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum Plasmodium falciparum ?
-
?
additional information the enzyme also performs the synthesis of (2E,6E)-farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.10, and of geranylgeranyl diphosphate from (2E,6E)-farnesyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.29. Product identification by thin layer chromatography and mass spectrometry Plasmodium falciparum ?
-
?
additional information a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum Plasmodium falciparum clone 3D7 ?
-
?
additional information the enzyme also performs the synthesis of (2E,6E)-farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.10, and of geranylgeranyl diphosphate from (2E,6E)-farnesyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.29. Product identification by thin layer chromatography and mass spectrometry Plasmodium falciparum clone 3D7 ?
-
?

Subunits

Subunits Comment Organism
? x * 70000, about, recombinant GST-tagged enzyme, SDS-PAGE Plasmodium falciparum

Synonyms

Synonyms Comment Organism
More cf. EC 2.5.1.29 and EC 2.5.1.10 Plasmodium falciparum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4 7.5 assay at Plasmodium falciparum

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics Plasmodium falciparum

General Information

General Information Comment Organism
physiological function the enzyme is a key enzyme in the metabolism of virtually all isoprenoids and it interconnects the 5-carbon moiety isoprenoid synthesis with the mid- or long-chained compound synthesis. The synthesis of farnesyl diphosphate and geranylgeranyl diphosphate is required for biosynthesis of ubiquinone, dolichol, carotenoids, menaquinone, tocopherol, and protein prenylation Plasmodium falciparum