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Literature summary 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

EC Number Application Comment Organism
2.5.1.29 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
2.5.1.92 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)

EC Number Cloned (Comment) Organism
2.5.1.29 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
2.5.1.92 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

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

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.5.1.29 additional information
-
 additional information Michaelis-Menten kinetics Plasmodium falciparum
2.5.1.29 0.00081
-
 isopentenyl diphosphate pH 7.5, 37°C, recombinant enzyme, with geranyl diphosphate Plasmodium falciparum
2.5.1.29 0.002
-
 isopentenyl diphosphate pH 7.5, 37°C, recombinant enzyme, with dimethylallyl diphosphate Plasmodium falciparum
2.5.1.29 0.0021
-
 (2E,6E)-farnesyl diphosphate pH 7.5, 37°C, recombinant enzyme, with isopentenyl diphosphate Plasmodium falciparum
2.5.1.29 0.0024
-
 isopentenyl diphosphate pH 7.5, 37°C, recombinant enzyme, with (2E,6E)-farnesyl diphosphate Plasmodium falciparum
2.5.1.29 0.0078
-
 geranyl diphosphate pH 7.5, 37°C, recombinant enzyme, with isopentenyl diphosphate Plasmodium falciparum
2.5.1.29 0.068
-
 dimethylallyl diphosphate pH 7.5, 37°C, recombinant enzyme, with isopentenyl diphosphate Plasmodium falciparum
2.5.1.92 additional information
-
 additional information Michaelis-Menten kinetics Plasmodium falciparum
2.5.1.92 0.002
-
 isopentenyl diphosphate pH 7.5, 37°C, recombinant enzyme, with dimethylallyl diphosphate Plasmodium falciparum
2.5.1.92 0.068
-
 dimethylallyl diphosphate pH 7.5, 37°C, recombinant enzyme, with isopentenyl diphosphate Plasmodium falciparum

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.5.1.29 Mg2+ required Plasmodium falciparum
2.5.1.92 Mg2+ required Plasmodium falciparum

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.5.1.29 70000
-
-
 Plasmodium falciparum
2.5.1.92 70000
-
-
 Plasmodium falciparum

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.29 Plasmodium falciparum Q8II79 gene PF3D7_1128400
-
2.5.1.29 Plasmodium falciparum clone 3D7 Q8II79 gene PF3D7_1128400
-
2.5.1.92 Plasmodium falciparum
-
 gene PF3D7_1128400
-
2.5.1.92 Plasmodium falciparum clone 3D7
-
 gene PF3D7_1128400
-

Purification (Commentary)

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

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.5.1.29 additional information the enzyme is constitutively expressed in all stages during the asexual intra-erythrocytic cycle of Plasmodium falciparum, overview Plasmodium falciparum
-
2.5.1.92 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)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.29 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
-
 Plasmodium falciparum diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.29 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
-
 Plasmodium falciparum clone 3D7 diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.29 dimethylallyl diphosphate + 2 isopentenyl diphosphate the enzyme also performs the synthesis of farnesyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.92 Plasmodium falciparum 2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
 ?
2.5.1.29 dimethylallyl diphosphate + 2 isopentenyl diphosphate the enzyme also performs the synthesis of farnesyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.92 Plasmodium falciparum clone 3D7 2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
 ?
2.5.1.29 geranyl diphosphate + isopentenyl diphosphate the enzyme also performs the synthesis of farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.10 Plasmodium falciparum diphosphate + (2E,6E)-farnesyl diphosphate
-
 ?
2.5.1.29 geranyl diphosphate + isopentenyl diphosphate the enzyme also performs the synthesis of farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate, reaction of EC 2.5.1.10 Plasmodium falciparum clone 3D7 diphosphate + (2E,6E)-farnesyl diphosphate
-
 ?
2.5.1.29 additional information a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum Plasmodium falciparum ?
-
 ?
2.5.1.29 additional information product identification by thin layer chromatography and mass spectrometry Plasmodium falciparum ?
-
 ?
2.5.1.29 additional information a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum Plasmodium falciparum clone 3D7 ?
-
 ?
2.5.1.29 additional information product identification by thin layer chromatography and mass spectrometry Plasmodium falciparum clone 3D7 ?
-
 ?
2.5.1.92 dimethylallyl diphosphate + 2 isopentenyl diphosphate
-
 Plasmodium falciparum 2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
 ?
2.5.1.92 dimethylallyl diphosphate + 2 isopentenyl diphosphate
-
 Plasmodium falciparum clone 3D7 2 diphosphate + (2Z,6Z)-farnesyl diphosphate
-
 ?
2.5.1.92 additional information a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum Plasmodium falciparum ?
-
 ?
2.5.1.92 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 ?
-
 ?
2.5.1.92 additional information a bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase exists in Plasmodium falciparum Plasmodium falciparum clone 3D7 ?
-
 ?
2.5.1.92 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

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

Synonyms

EC Number Synonyms Comment Organism
2.5.1.29 farnesyl diphosphate/geranylgeranyl diphosphate synthase
-
 Plasmodium falciparum
2.5.1.29 More cf. EC 2.5.1.92 and EC 2.5.1.10 Plasmodium falciparum
2.5.1.29 PfFPPS
-
 Plasmodium falciparum
2.5.1.29 PfGGPPS
-
 Plasmodium falciparum
2.5.1.92 More cf. EC 2.5.1.29 and EC 2.5.1.10 Plasmodium falciparum

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.5.1.29 37
-
 assay at Plasmodium falciparum
2.5.1.92 37
-
 assay at Plasmodium falciparum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.5.1.29 7.4 7.5 assay at Plasmodium falciparum
2.5.1.92 7.4 7.5 assay at Plasmodium falciparum

Ki Value [mM]

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

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.5.1.29 0.0013
-
 pH 7.5, 37°C, recombinant enzyme, versus FPP/IPP Plasmodium falciparum risedronate
2.5.1.29 0.01
-
 pH 7.5, 37°C, recombinant enzyme, versus GPP/IPP Plasmodium falciparum risedronate

General Information

EC Number General Information Comment Organism
2.5.1.29 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 the biosynthesis of ubiquinone, dolichol, carotenoids, menaquinone, tocopherol, and protein prenylation Plasmodium falciparum
2.5.1.92 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