Literature summary for 2.5.1.29 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.

Cloned(Commentary)

Cloned (Comment)	Organism
gene PVX_092040	Plasmodium vivax

Crystallization (Commentary)

Crystallization (Comment)	Organism
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

Crystallization (Comment)

Organism

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

Inhibitors	Comment	Organism
ibandronate	a nitrogen-containing bisphosphonate	Plasmodium vivax
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
zoledronate	a nitrogen-containing bisphosphonate	Plasmodium vivax
[1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonic acid	a nitrogen-containing bisphosphonate	Plasmodium vivax

KM Value [mM]

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

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Plasmodium vivax

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Plasmodium vivax	-	gene PVX_092040	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate	-	Plasmodium vivax	diphosphate + geranylgeranyl diphosphate	-	?
geranyl diphosphate + dimethylallyl diphosphate	-	Plasmodium vivax	diphosphate + geranylgeranyl diphosphate	-	?

Synonyms

Synonyms	Comment	Organism
geranylgeranyl pyrophosphate synthase	-	Plasmodium vivax
GGPP synthase	-	Plasmodium vivax
GGPPS	-	Plasmodium vivax

Temperature Optimum [°C]

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

Turnover Number [1/s]

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

pH Optimum

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

Ki Value [mM]

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

IC50 Value

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

kcat/KM [mM/s]

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