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Literature summary extracted from

  • Artz, J.D.; Wernimont, A.K.; Dunford, J.E.; Schapira, M.; Dong, A.; Zhao, Y.; Lew, J.; Russell, R.G.; Ebetino, F.H.; Oppermann, U.; Hui, R.
    Molecular characterization of a novel geranylgeranyl pyrophosphate synthase from Plasmodium parasites (2011), J. Biol. Chem., 286, 3315-3322.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.5.1.29 gene PVX_092040 Plasmodium vivax

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.5.1.29 purified recombinant GGPPS, in apo form or in complex with zoledronate, hanging drop vapour diffusion method, for the apo enzyme crystals: 0.0015 ml of 16.5 mg/ml protein in 10 mM HEPES, pH 7.5, 500 mM NaCl, is mixed with 0.0015 ml of reservoir solution containing 22% PEG 3350, 200 mM Li2SO4, 100 mM Tris, pH 8.5, for the inhibitor complex crystals: 0.0015 ml of 11.2 mg/ml protein and 10 mM zoledronate, 10 mM IPP, 10 mM MgCl2, 10 mM HEPES, pH 7.5, 500 mM NaCl are mixed with 0.0015 ml reservoir solution containing 20% PEG 3350, 200 mM Li2SO4, 100 mM Tris, 8.5, 18°C, overnight, X-ray diffraction structure determination and analysis at 2.1 A resolution Plasmodium vivax

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.29 ibandronate a nitrogen-containing bisphosphonate Plasmodium vivax
2.5.1.29 nitrogen-containing bisphosphonates Plasmodium vivax GGPP synthase can bind nitrogen-containing bisphosphonates strongly with the energetically favorable cooperation of three Mg2+, resulting in inhibition at IC50 concentrations below 100 nM. The aspartates at the start and end of the five-residue motif, the second aspartate-rich motif, in Plasmodium vivax GGPPSs both participate in the coordination of the third Mg2+ Plasmodium vivax
2.5.1.29 zoledronate a nitrogen-containing bisphosphonate Plasmodium vivax
2.5.1.29 [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonic acid a nitrogen-containing bisphosphonate Plasmodium vivax

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.5.1.29 0.0019
-
 geranyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.0032
-
 dimethylallyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.0073
-
 (2E,6E)-farnesyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.0084
-
 isopentenyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax

Metals/Ions

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.29 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate Plasmodium vivax
-
 diphosphate + geranylgeranyl diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.29 Plasmodium vivax
-
 gene PVX_092040
-

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 vivax diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.29 geranyl diphosphate + dimethylallyl diphosphate
-
 Plasmodium vivax diphosphate + geranylgeranyl diphosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.29 geranylgeranyl pyrophosphate synthase
-
 Plasmodium vivax
2.5.1.29 GGPP synthase
-
 Plasmodium vivax
2.5.1.29 GGPPS
-
 Plasmodium vivax

Temperature Optimum [°C]

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

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.5.1.29 0.5
-
 dimethylallyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.5
-
 geranyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.8
-
 (2E,6E)-farnesyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.8
-
 isopentenyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.5.1.29 7.7
-
 assay at Plasmodium vivax

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.5.1.29 0.0000107
-
 zoledronate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.0000124
-
 [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonic acid pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 0.000016
-
 ibandronate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.5.1.29 0.0000433
-
 pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax zoledronate
2.5.1.29 0.0000475
-
 pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonic acid
2.5.1.29 0.0000619
-
 pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax ibandronate

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.5.1.29 100
-
 (2E,6E)-farnesyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 200
-
 dimethylallyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax
2.5.1.29 300
-
 geranyl diphosphate pH 7.7, 37°C, recombinant PvGGPPS Plasmodium vivax