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drug target
antimalarial drug target
drug target
due to its crucial role in isoprenoid biosynthesis, the enzyme is a molecular target for the treatment of different bone disorders and to control parasitic diseases, particularly, those produced by trypanosomatids and Apicomplexan parasites. Notwithstanding their lack of drug-like character, bisphosphonates are the most advantageous class of inhibitors of the enzymatic activity of farnesyl pyrophosphate synthase. The poor drug-like character is largely compensated by the high affinity of the bisphosphonate moiety by bone mineral hydroxyapatite in humans. Several bisphosphonates are currently in use for the treatment of a variety of bone disorders. Currently, the great prospects that bisphosphonates behave as antiparasitic agents is due to their accumulation in acidocalcisomes, organelles with equivalent composition to bone mineral, hence facilitating their antiparasitic action
drug target
farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway and a good candidate for drug design
drug target
farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway and a good candidate for drug design
drug target
the enzyme is a drug target for the treatment of cutaneous leishmaniasis
drug target
the enzyme is a target for treating bone resorption diseases and some cancers
drug target
the enzyme plays a significant role in the disease-related cell signaling pathway, and the inhibition of the enzyme is a potential approach for treating FPPS-regulated diseases
drug target
Trypanosoma brucei is the causative agent of human African trypanosomiasis. Nitrogen-containing bisphosphonates, a current treatment for bone diseases, have been shown to block the growth of the Trypanosoma brucei parasites by inhibiting farnesyl pyrophosphate synthase. However, due to their poor pharmacokinetic properties, they are not well suited for antiparasitic therapy. Tthe discovery of new binding sites and non-bisphosphonate binders is a critical step towards the investigation of farnesyl pyrophosphate synthase as a drug target for human African trypanosomiasis and opens up the possibility of a fragment-to-lead optimisation program
drug target
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the enzyme is a drug target for the treatment of cutaneous leishmaniasis
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drug target
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farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway and a good candidate for drug design
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evolution
Giardia and Leishmania farnesyl diphosphate synthase enzymes are phylogenetically distant but display conserved protein signatures. The nitrogen-containing bisphosphonates effect on farnesyl diphosphate synthase is more pronounced in Leishmania than Giardia. This might be due to general differences in metabolism and differences in the farnesyl diphosphate synthase catalytic site
evolution
Giardia and Leishmania farnesyl diphosphate synthase enzymes are phylogenetically distant but display conserved protein signatures. The nitrogen-containing bisphosphonates effect on farnesyl diphosphate synthase is more pronounced in Leishmania than Giardia. This might be due to general differences in metabolism and differences in the farnesyl diphosphate synthase catalytic site
evolution
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reported of the molecular evolution of positive selection sites in plant. Gene expression analysis shows that FPS genes could increase terpenoid accumulation in plants. Large-scale evolutionary analysis of farnesyl diphosphate synthase in land plants. It explores the relationship between the molecular evolution of positive selection sites and their roles in plant farnesyl diphosphate synthase. Farnesyl diphosphate synthase genes in plants appeared very early, and can be traced back to the bryophyte divergence to pteridophyte, which then evolves into gymnospermae, monocotyledonae, and dicotyledoneae. A number of signals for positive selection exist in plant farnesyl diphosphate synthases. Thirty-nine positively selected sites in the site model and three positively selected sites in the branch-site model are detected, respectively
evolution
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reported of the molecular evolution of positive selection sites in plant. Gene expression analysis shows that FPS genes could increase terpenoid accumulation in plants. Large-scale evolutionary analysis of farnesyl diphosphate synthase in land plants. It explores the relationship between the molecular evolution of positive selection sites and their roles in plant farnesyl diphosphate synthase. Farnesyl diphosphate synthase genes in plants appeared very early, and can be traced back to the bryophyte divergence to pteridophyte, which then evolves into gymnospermae, monocotyledonae, and dicotyledoneae. A number of signals for positive selection exist in plant farnesyl diphosphate synthases. Thirty-nine positively selected sites in the site model and three positively selected sites in the branch-site model are detected, respectively
evolution
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reported of the molecular evolution of positive selection sites in plant. Gene expression analysis shows that FPS genes could increase terpenoid accumulation in plants. Large-scale evolutionary analysis of farnesyl diphosphate synthase in land plants. It explores the relationship between the molecular evolution of positive selection sites and their roles in plant farnesyl diphosphate synthase. Farnesyl diphosphate synthase genes in plants appeared very early, and can be traced back to the bryophyte divergence to pteridophyte, which then evolves into gymnospermae, monocotyledonae, and dicotyledoneae. A number of signals for positive selection exist in plant farnesyl diphosphate synthases. Thirty-nine positively selected sites in the site model and three positively selected sites in the branch-site model are detected, respectively
evolution
reported of the molecular evolution of positive selection sites in plant. Gene expression analysis shows that FPS genes could increase terpenoid accumulation in plants. Large-scale evolutionary analysis of farnesyl diphosphate synthase in land plants. It explores the relationship between the molecular evolution of positive selection sites and their roles in plant farnesyl diphosphate synthase. Farnesyl diphosphate synthase genes in plants appeared very early, and can be traced back to the bryophyte divergence to pteridophyte, which then evolves into gymnospermae, monocotyledonae, and dicotyledoneae. A number of signals for positive selection exist in plant farnesyl diphosphate synthases. Thirty-nine positively selected sites in the site model and three positively selected sites in the branch-site model are detected, respectively
evolution
reported of the molecular evolution of positive selection sites in plant. Gene expression analysis shows that FPS genes could increase terpenoid accumulation in plants. Large-scale evolutionary analysis of farnesyl diphosphate synthase in land plants. It explores the relationship between the molecular evolution of positive selection sites and their roles in plant farnesyl diphosphate synthase. Farnesyl diphosphate synthase genes in plants appeared very early, and can be traced back to the bryophyte divergence to pteridophyte, which then evolves into gymnospermae, monocotyledonae, and dicotyledoneae. A number of signals for positive selection exist in plant farnesyl diphosphate synthases. Thirtynine positively selected sites in the site model and three positively selected sites in the branch-site model are detected, respectively
evolution
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Giardia and Leishmania farnesyl diphosphate synthase enzymes are phylogenetically distant but display conserved protein signatures. The nitrogen-containing bisphosphonates effect on farnesyl diphosphate synthase is more pronounced in Leishmania than Giardia. This might be due to general differences in metabolism and differences in the farnesyl diphosphate synthase catalytic site
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malfunction
inhibition of the enzyme by nitrogen-containing bisphosphonates (N-BPs) can cause a shortage of geranyl diphosphate, farnesyl diphosphate and geranylgeranyl diphosphate, which are intermediate metabolites involved in the regulation of cellular functions and homeostasis. A shortage of farnesyl diphosphate can cause failure in the isoprenylation of proteins as well as the nuclear lamina and Rab GTPases that are anchored in the intracellular region of the plasma membrane. The nuclear lamina and Rab GTPases interfere with the vesicular transport, endocytosis and exocytosis. Deficits in the synthesis of dolichol interfere with asparagine (N)-linked glycosylation that regulates numerous cellular activities such as glycoprotein quality control, intracellular trafficking and cell-cell communications (disorganization of intracellular membranes culminating in Leishmania apoptosis)
malfunction
inhibition of the enzyme by nitrogen-containing bisphosphonates (N-BPs) can cause a shortage of geranyl diphosphate, farnesyl diphosphate and geranylgeranyl diphosphate, which are intermediate metabolites involved in the regulation of cellular functions and homeostasis. A shortage of farnesyl diphosphate can cause failure in the isoprenylation of proteins as well as the nuclear lamina and Rab GTPases that are anchored in the intracellular region of the plasma membrane. The nuclear lamina and Rab GTPases interfere with the vesicular transport, endocytosis and exocytosis. Deficits in the synthesis of dolichol interfere with asparagine (N)-linked glycosylation that regulates numerous cellular activities such as glycoprotein quality control, intracellular trafficking and cell-cell communications (disorganization of intracellular membranes culminating in Leishmania apoptosis)
malfunction
knockdown of MpFPPS1 and MpFPPS2 imposes no effect on mortality, but gene knockdown significantly increases the fecundity (no. of offspring) per aphid. Knockdown of MpFPPS1 and MpFPPS2 significantly decreases the proportion of aphid emitting cornicle droplets by 24.9% and 24.0%, respectively, in response to artificial stimulation
malfunction
knockdown of MpFPPS1 and MpFPPS2 imposes no significant cost on mortality, but gene knockdown significantly increases the fecundity (no. of offspring) per aphid. Knockdown of MpFPPS1 and MpFPPS2 significantly decreases the proportion of aphid emitting cornicle droplets by 24.9% and 24.0%, respectively, in response to artificial stimulation
malfunction
slow growth of an Escherichia coli ispA null mutant lacking farnesyl diphosphate synthase. The growth rates of ispA mutant-transformants harboring a medium-copy number plasmid that carries ispA is almost the same as that of the wild-type strain
malfunction
the blockade of farnesyl pyrophosphate synthase prevents the synthesis of farnesyl diphosphate and the downstream essential products
malfunction
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slow growth of an Escherichia coli ispA null mutant lacking farnesyl diphosphate synthase. The growth rates of ispA mutant-transformants harboring a medium-copy number plasmid that carries ispA is almost the same as that of the wild-type strain
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malfunction
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inhibition of the enzyme by nitrogen-containing bisphosphonates (N-BPs) can cause a shortage of geranyl diphosphate, farnesyl diphosphate and geranylgeranyl diphosphate, which are intermediate metabolites involved in the regulation of cellular functions and homeostasis. A shortage of farnesyl diphosphate can cause failure in the isoprenylation of proteins as well as the nuclear lamina and Rab GTPases that are anchored in the intracellular region of the plasma membrane. The nuclear lamina and Rab GTPases interfere with the vesicular transport, endocytosis and exocytosis. Deficits in the synthesis of dolichol interfere with asparagine (N)-linked glycosylation that regulates numerous cellular activities such as glycoprotein quality control, intracellular trafficking and cell-cell communications (disorganization of intracellular membranes culminating in Leishmania apoptosis)
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metabolism
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the enzyme supplies precursors for highly branched isoprenoid biosynthesis
metabolism
both FPPS genes are involved in the production of alarm pheromone EbetaF in Myzus persicae and cornicle droplet emission is closely associated with the EbetaF release in the aphid
metabolism
farnesyl diphosphate synthase is a key enzyme responsible for the supply of isoprenoid precursors for several essential metabolites, including sterols, dolichols and ubiquinone
metabolism
farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway
metabolism
farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway
metabolism
produces geranylgeranyl diphosphate for the synthesis of carotenoids in the chloroplast
metabolism
the bifunctional farnesyl/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key branchpoint enzyme in isoprenoid biosynthesis in Plasmodium falciparum (malaria) parasites
metabolism
the enzyme catalyzes the formation of farnesyl pyrophosphate, a key intermediate for the biosynthesis of all isoprenoids
metabolism
the enzyme is a key regulator of the mevalonate pathway
metabolism
the enzyme is present in all organisms and constitutes a key enzyme within the mevalonate pathway and the isoprenoid synthesis. It catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give rise to one molecule of geranyl diphosphate, which on a further reaction with another molecule of isopentenyl diphosphate forms the 15-carbon isoprenoid farnesyl diphosphate. This molecule is the obliged precursor for the biosynthesis of sterols, ubiquinones, dolichols, heme A, and prenylated proteins
metabolism
the enzyme plays a key role in the biosynthesis of the morphogenetic and gonadotropic juvenile hormone
metabolism
under environmental stresses, Haematococcus pluvialis accumulates large amounts of carotenoids. Scale of carotenoid biosynthesis depends on availability of geranylgeranyl pyrophosphate precursor, which is supplied by geranylgeranyl pyrophosphate synthase through sequential 1'-4 condensation of three isopentenyl pyrophosphates into dimethylallyl pyrophosphate. Transcription of geranylgeranyl pyrophosphate synthase genes, morphological transformation, and carotenoid biosynthesis are differentially induced by environmental stresses, while the products of the enzyme are low in vivo, implying that most of prenyl pyrophosphate flux is shunted into carotenoid biosynthesis
metabolism
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farnesyl diphosphate synthase is a key enzyme responsible for the supply of isoprenoid precursors for several essential metabolites, including sterols, dolichols and ubiquinone
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metabolism
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the enzyme supplies precursors for highly branched isoprenoid biosynthesis
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metabolism
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the enzyme catalyzes the formation of farnesyl pyrophosphate, a key intermediate for the biosynthesis of all isoprenoids
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metabolism
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farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway
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physiological function
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shRNA-mediated knock-down of expression results in conversion of hematopoietic and nonhematopoietic tumor cell lines into Vgamma9Vdelta2 T-cell activators. Knock-down cells activate Vgamma9Vdelta2 cells. Vgamma9Vdelta2 cells act as sensors of a dysregulated isoprenoid metabolism, therapeutic down-modulation of FPPS expression may be used as a tool to target tumor cells to Vgamma9Vdelta2 T-cell mediated immunosurveillance
physiological function
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twelve weeks of treatment with inhibitor alendronate attenuates the left ventricular weight to body weight ratio, hydroxyproline content, collagen deposition in the interstitia, and gene expression of atrial natriuretic peptide, B-type natriuretic peptide, and procollagen type I/III in the SHR left ventricle, all of which are significantly higher in spontaneously hypertensive rats than in control rats. Long-term treatment with inhibitor significantly reduces RhoA activation, ERK phosphorylation, and TGF-b1 expression in the spontaneously hypertensive rat left ventricle, all ofwhich were upregulated more in spontaneously hypertensive rats than in control rats
physiological function
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the enzyme is involved in the biosynthesis of the monoterpenoid precursors needed for formation of the defensive compound chrysomelidial
physiological function
the enzyme regulates the volatile sesquiterpenes in wintersweet flower
physiological function
both transient and stable overexpression of geranyl(geranyl) diphosphate synthase G(G)PPS and coexpression of G(G)PPS plus geraniol synthase GES significantly enhances the accumulation of secologanin, which in turn elevates the levels of monomeric monoterpene indole alkaloids. Transgenic plants exhibit increased levels of root alkaloid ajmalicine. The dimeric alkaloid vinblastine is enhanced only in G(G)PPS but not in G(G)PPS plus GES transgenic lines, correlating with transcript levels of peroxidase PRX1 involved in coupling of vindoline and catharanthine into 3',4'-anhydrovinblastine
physiological function
both FPPS genes (MpFPPS1 and MpFPPS2) are involved in the production of alarm pheromone EbetaF in Myzus persicae and cornicle droplet emission is closely associated with the EbetaF release in the aphid
physiological function
farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major
physiological function
key enzyme responsible for the supply of isoprenoid precursors for several essential metabolites, including sterols, dolichols and ubiquinone
physiological function
the enzyme performs a regulatory role in triterpene biosynthesis
physiological function
under environmental stresses, Haematococcus pluvialis accumulates large amounts of carotenoids. Scale of carotenoid biosynthesis depends on availability of geranylgeranyl pyrophosphate precursor, which is supplied by geranylgeranyl pyrophosphate synthase through sequential 1'-4 condensation of three isopentenyl pyrophosphates into dimethylallyl pyrophosphate. Transcription of geranylgeranyl pyrophosphate synthase genes, morphological transformation, and carotenoid biosynthesis are differentially induced by environmental stresses, while the products of the enzyme are low in vivo, implying that most of prenyl pyrophosphate flux is shunted into carotenoid biosynthesis
physiological function
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key enzyme responsible for the supply of isoprenoid precursors for several essential metabolites, including sterols, dolichols and ubiquinone
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physiological function
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farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major
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