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drug target
antimalarial drug target
drug target
the enzyme is a target for treating bone resorption diseases and some cancers
evolution
Jc-GGPPS is a member of the polyprenyltransferases with two highly conserved aspartate-rich motifs, and shows high homology to other plant GGPPSs, phylogenetic analysis, overview. Jc-GGPPS has closer relationship with angiosperm plant GGPPSs
evolution
the enzyme from Catharanthus roseus is a plant type II GGPS belonging to the short-chain prenyltransferase subfamily
evolution
Euglena gracilis CrtE belongs to a clade that is distinct from groups of algae and higher plants
evolution
fungi-derived GGPPSs can be divided into three clusters, suggesting there are three types of GGPPSs in fungi. Each type may be responsible for a different metabolism. The three types of GGPPSs from Cordyceps militaris belong to the different clusters separately
evolution
fungi-derived GGPPSs can be divided into three clusters, suggesting there are three types of GGPPSs in fungi. Each type may be responsible for a different metabolism. The three types of GGPPSs from Cordyceps militaris belong to the different clusters separately. Isozyme GGPPS191 contains all five domains highly conserved among prenyltransferases as well as two aspartate-rich DDXX(XX)D motifs in domains II and V, which have been proven essential for prenyltransferase activity
evolution
fungi-derived GGPPSs can be divided into three clusters, suggesting there are three types of GGPPSs in fungi. Each type may be responsible for a different metabolism. The three types of GGPPSs from Cordyceps militaris belong to the different clusters separately. Isozyme GGPPS727 contains all five domains highly conserved among prenyltransferases as well as two aspartate-rich DDXX(XX)D motifs in domains II and V, which have been proven essential for prenyltransferase activity
evolution
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phylogenetic analysis of characterized and putative prenyltransferases, overview
evolution
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the enzyme is a member of a group of polyprenyltransferases with five conserved domains and two highly conserved aspartate-rich motifs
evolution
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Euglena gracilis CrtE belongs to a clade that is distinct from groups of algae and higher plants
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evolution
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phylogenetic analysis of characterized and putative prenyltransferases, overview
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malfunction
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depletion of geranylgeranyl diphosphate by inhibitor statins leads to accumulation of farnesyl diphosphate, which activates nuclear hormone receptors stimulating osteoblast differentiation and bone formation. Statins directly inhibit HMG-CoA reductase, the first step of the isoprenoid biosynthesis pathway
malfunction
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crtE overexpression compensates for the lack of IdsA, whereas plasmid-borne overexpression of ispB does not
malfunction
inefficient substrate channeling between Erg20p and Bts1p results in farnesyl diphosphate accumulation, which in turn leads to feedback inhibition or precursor drain through competing reactions (sterol biosynthesis, dephosphorylation, or other)
malfunction
reduced GGPPS11 levels in the ggpps11-5 allele result in pale plants with smaller mesophyll chloroplasts. Levels of chlorophylls (a and b), carotenoids (beta-carotene, violaxanthin, neoxanthin, and lutein) and prenylquinones such as tocopherols (alpha-tocopherol and gamma-tocopherol), plastoquinones (plastochromanol-8 and plastoquinone-9) and phylloquinone are significantly reduced in ggpps11-5 seedlings, whereas complemented lines show a metabolite profile similar to that of wild-type controls, phenotype, overview
malfunction
specific deletion of geranylgeranyl diphosphate synthase 1 (Ggps1) in lung epithelium during fetal lung development results in neonatal respiratory distress syndrome-like disease. The knockout mice die at postnatal day 1 of respiratory failure, and the lungs show compensatory pneumonectasis, pulmonary atelectasis, and hyaline membranes. Lung malformations in Ggps1-deficient mice result from the failure of fetal lung branching morphogenesis. Ggps1 deletion blocks K-Ras geranylgeranylation and extracellular signal-related kinase 1 or 2/mitogen-activated protein kinase signaling, which in turn disturbs fibroblast growth factor 10 regulation on fetal lung branching morphogenesis. Ggps1 deficiency inhibits KRas/MAPK signaling, which in turn abrogates FGF10 regulation on fetal lung morphogenesis, phenotype, overview
malfunction
the two T-DNA insertion mutant alleles, ggps1-2 and ggps1-3, result in seedling lethal albino and embryo-lethal phenotypes, respectively. Mutations in geranylgeranyl diphosphate synthase 1 affect chloroplast development in Arabidopsis thaliana. Temperature-sensitive leaf variegation mutant ggps1-1 is caused by a point mutation. Total chlorophyll and carotenoid levels are reduced in ggps1-1 white tissues as compared with green tissues. The ggps1-1 green sector photosynthetic rate is not elevated relative to wild-type tissues. Chloroplast development in green sectors of mutated leaves appear normal, whereas cells in white sectors contain abnormal plastids with numerous electron translucent bodies and poorly developed internal membranes. Mutant ggps1-1 phenotype, detailed overview
malfunction
yeast geranylgeranyl diphosphate synthase becomes an inactive monomer when the first N-terminal helix involved in dimerization is deleted
malfunction
crtE knockout mutants are white, in contrast to the light orange color of the wild-type strains
malfunction
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direct silencing of geranylgeranyl diphosphate synthase decreases the carotenoid content
malfunction
knockdown of geranylgeranyl diphosphate synthase inhibits the migration and invasion of lung adenocarcinoma cells, but does not affect cell proliferation and apoptosis. Geranylgeranyl diphosphate synthase inhibition significantly increases the expression of E-cadherin and reduces the expression of N-cadherin and vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42 geranylgeranylation is reduced by geranylgeranyl diphosphate synthase knockdown
malfunction
the bifunctional farnesyl/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key branchpoint enzyme in isoprenoid biosynthesis
malfunction
the loss of Ggpps causes disorganized cardiac cytoarchitecture as early as E11.5 by disturbing cell-cell junctions. Ggpps inactivation decreases Rho GTPase geranylgeranylation and their activity, which might account for the disruption of cell-cell junctions
malfunction
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the bifunctional farnesyl/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key branchpoint enzyme in isoprenoid biosynthesis
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malfunction
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crtE overexpression compensates for the lack of IdsA, whereas plasmid-borne overexpression of ispB does not
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malfunction
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specific deletion of geranylgeranyl diphosphate synthase 1 (Ggps1) in lung epithelium during fetal lung development results in neonatal respiratory distress syndrome-like disease. The knockout mice die at postnatal day 1 of respiratory failure, and the lungs show compensatory pneumonectasis, pulmonary atelectasis, and hyaline membranes. Lung malformations in Ggps1-deficient mice result from the failure of fetal lung branching morphogenesis. Ggps1 deletion blocks K-Ras geranylgeranylation and extracellular signal-related kinase 1 or 2/mitogen-activated protein kinase signaling, which in turn disturbs fibroblast growth factor 10 regulation on fetal lung branching morphogenesis. Ggps1 deficiency inhibits KRas/MAPK signaling, which in turn abrogates FGF10 regulation on fetal lung morphogenesis, phenotype, overview
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malfunction
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reduced GGPPS11 levels in the ggpps11-5 allele result in pale plants with smaller mesophyll chloroplasts. Levels of chlorophylls (a and b), carotenoids (beta-carotene, violaxanthin, neoxanthin, and lutein) and prenylquinones such as tocopherols (alpha-tocopherol and gamma-tocopherol), plastoquinones (plastochromanol-8 and plastoquinone-9) and phylloquinone are significantly reduced in ggpps11-5 seedlings, whereas complemented lines show a metabolite profile similar to that of wild-type controls, phenotype, overview
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malfunction
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the two T-DNA insertion mutant alleles, ggps1-2 and ggps1-3, result in seedling lethal albino and embryo-lethal phenotypes, respectively. Mutations in geranylgeranyl diphosphate synthase 1 affect chloroplast development in Arabidopsis thaliana. Temperature-sensitive leaf variegation mutant ggps1-1 is caused by a point mutation. Total chlorophyll and carotenoid levels are reduced in ggps1-1 white tissues as compared with green tissues. The ggps1-1 green sector photosynthetic rate is not elevated relative to wild-type tissues. Chloroplast development in green sectors of mutated leaves appear normal, whereas cells in white sectors contain abnormal plastids with numerous electron translucent bodies and poorly developed internal membranes. Mutant ggps1-1 phenotype, detailed overview
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malfunction
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crtE knockout mutants are white, in contrast to the light orange color of the wild-type strains
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metabolism
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CrtE catalyzes one of the first steps in the carotenogenic pathway, overview
metabolism
GGPP is one of the key precursors in the biosynthesis of biologically significant isoprenoid compounds
metabolism
role of SmGGPPS involved in the tanshinones biosynthesis pathway, overview
metabolism
the enzyme geranylgeranyl diphosphate synthase from Catharanthus roseus catalyses the formation of geranylgeranyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate via three successive condensation reactions, exhibiting the activities of EC 2.5.1.1, EC 2.5.1.10, and EC 2.5.1.29
metabolism
biosynthesis of sclareol from geranylgeranyl diphosphate, overview
metabolism
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both Corynebacterium glutamicum enzymes, IdsA and CrtE, catalyze prenyl transfer with isopentenyl diphosphate (IPP), dimethylallyl diphosphate, geranyl diphosphate and farnesyl phosphate as substrates. The enzymes are part of the carotenoid biosynthesis pathway, but CrtE is not required for carotenogenesis in Corynebacterium glutamicum. IdsA shows the highest catalytic efficiency with dimethylallyl diphosphate and IPP, whereas the catalytic efficiency of CrtE is highest with geranyl diphosphate and IPP
metabolism
geranylgeranyl diphosphate is synthesized in different compartments by GGPP synthase (GGPPS) enzymes (the numbers refer to the Arabidopsis thaliana isoforms). Some of the enzymes channel geranylgeranyl diphosphate to specific isoprenoid pathways, isoprenoid biosynthesis in plant cell compartments, overview
metabolism
geranylgeranyl diphosphate synthase is a key enzyme in the carotenoid biosynthetic pathway, catalyzing the synthesis of its C20 precursor
metabolism
geranylgeranyl diphosphate synthase is a key enzyme in the carotenoid biosynthetic pathway, catalyzing the synthesis of its C20 precursor. Isozyme GGPPS 727 may be responsible for primary metabolism
metabolism
the enzyme catalyzes an early step of carotenoid biosynthesis
metabolism
the enzyme catalyzes the entrance step in the deinoxanthin biosynthetic pathway
metabolism
the enzyme is involved in biosynthesis of cyclooctatin
metabolism
the enzyme is involved in the astaxanthin biosynthesis 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 facilitates the organization of cardiomyocytes during mid-gestation through modulating protein geranylgeranylation in mouse heart
metabolism
the enzyme is involved in the mevalonate pathway
metabolism
the enzyme participates in the astaxanthin biosynthesis
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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the enzyme catalyzes an early step of carotenoid biosynthesis
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metabolism
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both Corynebacterium glutamicum enzymes, IdsA and CrtE, catalyze prenyl transfer with isopentenyl diphosphate (IPP), dimethylallyl diphosphate, geranyl diphosphate and farnesyl phosphate as substrates. The enzymes are part of the carotenoid biosynthesis pathway, but CrtE is not required for carotenogenesis in Corynebacterium glutamicum. IdsA shows the highest catalytic efficiency with dimethylallyl diphosphate and IPP, whereas the catalytic efficiency of CrtE is highest with geranyl diphosphate and IPP
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metabolism
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the enzyme catalyzes the entrance step in the deinoxanthin biosynthetic pathway
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metabolism
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the enzyme is involved in the astaxanthin biosynthesis pathway
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metabolism
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geranylgeranyl diphosphate is synthesized in different compartments by GGPP synthase (GGPPS) enzymes (the numbers refer to the Arabidopsis thaliana isoforms). Some of the enzymes channel geranylgeranyl diphosphate to specific isoprenoid pathways, isoprenoid biosynthesis in plant cell compartments, overview
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metabolism
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the enzyme is involved in biosynthesis of cyclooctatin
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metabolism
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CrtE catalyzes one of the first steps in the carotenogenic pathway, overview
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physiological function
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influence on plaunotol biosynthesis
physiological function
Vitis vinifera x Vitis vinifera
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involved in terpenoid metabolism
physiological function
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involved in terpenoid metabolism
physiological function
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isoform PaxG is required for paxilline biosynthesis
physiological function
biosynthesis of geranylgeranyl diphosphate, a precursor for the ether-linked lipids
physiological function
geranylgeranyl diphosphate is synthesized as diterpene defensive secretion used as chemical weapon of termite soldiers. GGPP is also used for various other essential cellular roles in animals. It plays an essential role in various processes such as electron transport (e.g., ubiquinones), glycosylation (e.g., dolichols), and membrane association (prenylation of proteins: e.g., geranylgeranylated proteins), as well as in secondary metabolites such as carotenoids
physiological function
geranylgeranyl diphosphate synthase catalyzes the biosynthesis of geranylgeranyl diphosphate, which is a key precursor for diterpenes including tanshinone. SmGGPPS is elicitor-responsive
physiological function
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the enzyme is required for synthesis of geranylgeranyl diphosphate which is required for e.g. Rap1a geranylgeranylation
physiological function
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the primary cellular use of geranylgeranyl diphosphate in humans is post-translational incorporation into proteins, a process known as geranylgeranylation. proteins modified post-translationally by geranylgeranylation are implicated in numerous cellular processes related to human disease, e.g. geranylgeranylation of Rab27B is required for the formation of xenograft tumors in the breast cancer cell line MCF-7. Isoprenoids regulate geranylgeranyl diphosphate synthesis through several feedback mechanisms, overview
physiological function
enzyme geranylgeranyl diphosphate synthase catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate, with allylic diphosphates to generate the C20 prenyl chain used for protein prenylation and diterpenoid biosynthesis
physiological function
gene GGPPS11, encoding the only plastid isozyme essential for plant development, functions as a hub gene among GGPPS paralogues and is required for the production of all major groups of plastid isoprenoids. Both gene co-expression and protein-protein interaction likely contribute to the channeling of geranylgeranyl diphosphate by GGPPS11. Metabolite analysis confirms the essential role of GGPPS11 in plastid isoprenoid metabolism. Isozyme GGPPS11 interacts with plastid enzymes that use geranylgeranyl diphosphate as substrate
physiological function
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geranylgeranyl diphosphate synthase catalyzes the biosynthesis of geranylgeranyl diphosphate, a key precursor for carotenoid biosynthesis
physiological function
geranylgeranyl diphosphate synthase is a key enzyme in the isoprenoid biosynthetic pathway that catalyzes the formation of geranylgeranyl diphosphate, a precursor molecule to several biochemical pathways including those that lead into the biosynthesis of carotenoids and abscisic acid, prenyllipids such as the chlorophylls, and diterpenes such as gibberellic acid, in chlorplasts. GGPS1 is an essential key gene in the chlorophyll biosynthetic pathway
physiological function
geranylgeranyl diphosphate synthase modulates fetal lung branching morphogenesis possibly through controlling K-Ras prenylation. Enzyme GGPPS-controlled K-Ras prenylation and Erk1/2/MAPK signaling mediates FGF signaling on lung branching morphogenesis. FGF10 signaling is a principal pathway in regulating the development of various organs, including lung, mammary gland, kidney, and prostate
physiological function
geranylgeranyl pyrophosphate synthase is a key enzyme for a structurally diverse class of isoprenoid biosynthetic metabolites including gibberellins, carotenoids, chlorophylls and rubber
physiological function
GGPP synthase catalyzes all three isopentenyl diphosphate additions to dimethylally diphosphate, carrying out in the same active site the reactions catalyzed by both Erg20p (farnesyl diphosphate synthase, EC 2.5.1.10) and Bts1p (geranylgeranyl diphosphate synthase, EC 2.5.1.29)
physiological function
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IdsA is the major GGPPS of Corynebacterium glutamicum
physiological function
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IdsA is the major GGPPS of Corynebacterium glutamicum. CrtE overexpression compensates for the lack of IdsA, whereas plasmid-borne overexpression of ispB does not
physiological function
the amino acid composition of and around the first aspartate-rich motif of the enzyme is vital for GGPP synthase function. Enzyme DR1395 functions as GGPPS to provide GGPP for the biosynthesis of phytoene and then lycopene
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
physiological function
the formation of geranylgeranyl diphosphate is a key step in biosynthetic pathway of carotenoids and many other terpenes. This step is catalyzed by geranylgeranyl diphosphate synthase. Expression of enzyme-encoding gene IbGGPS is likely associated with carotenoid profiles in storage roots. Sweet potato geranylgeranyl pyrophosphate synthase gene IbGGPS increases carotenoid content and enhances osmotic stress tolerance in Arabidopsis thaliana
physiological function
essential enzyme in the biosynthesis of prenyl precursors for the production of primary and secondary metabolites, including sterols, dolichols, carotenoids and ubiquinones, and for the modification of proteins
physiological function
the enzyme is involved in Cyanobacterial terpenoid 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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biosynthesis of geranylgeranyl diphosphate, a precursor for the ether-linked lipids
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physiological function
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IdsA is the major GGPPS of Corynebacterium glutamicum
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physiological function
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IdsA is the major GGPPS of Corynebacterium glutamicum. CrtE overexpression compensates for the lack of IdsA, whereas plasmid-borne overexpression of ispB does not
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physiological function
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the amino acid composition of and around the first aspartate-rich motif of the enzyme is vital for GGPP synthase function. Enzyme DR1395 functions as GGPPS to provide GGPP for the biosynthesis of phytoene and then lycopene
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physiological function
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geranylgeranyl diphosphate synthase modulates fetal lung branching morphogenesis possibly through controlling K-Ras prenylation. Enzyme GGPPS-controlled K-Ras prenylation and Erk1/2/MAPK signaling mediates FGF signaling on lung branching morphogenesis. FGF10 signaling is a principal pathway in regulating the development of various organs, including lung, mammary gland, kidney, and prostate
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physiological function
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gene GGPPS11, encoding the only plastid isozyme essential for plant development, functions as a hub gene among GGPPS paralogues and is required for the production of all major groups of plastid isoprenoids. Both gene co-expression and protein-protein interaction likely contribute to the channeling of geranylgeranyl diphosphate by GGPPS11. Metabolite analysis confirms the essential role of GGPPS11 in plastid isoprenoid metabolism. Isozyme GGPPS11 interacts with plastid enzymes that use geranylgeranyl diphosphate as substrate
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physiological function
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geranylgeranyl diphosphate synthase is a key enzyme in the isoprenoid biosynthetic pathway that catalyzes the formation of geranylgeranyl diphosphate, a precursor molecule to several biochemical pathways including those that lead into the biosynthesis of carotenoids and abscisic acid, prenyllipids such as the chlorophylls, and diterpenes such as gibberellic acid, in chlorplasts. GGPS1 is an essential key gene in the chlorophyll biosynthetic pathway
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physiological function
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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
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physiological function
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the enzyme is involved in Cyanobacterial terpenoid biosynthesis
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additional information
GGPPS gene can be a good model to study the regulatory mechanisms controlling phorbol esters accumulation at the transcriptional level
additional information
enzyme structure homology modelling and structure comparisons, overview
additional information
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enzyme structure homology modelling and structure comparisons, overview
additional information
enzyme-substrate docking using the crystal structure of human GGPPase, PDB ID 2Q80PDB
additional information
HaGGPS expression alters gibberellin levels in transgenic tobacco lines
additional information
molecular homology modeling with CfGGPPS as model sequence and PDB entries 2E8V and 2Q80 (yeast and human GGPPSs) as templates, ligand binding analysis, overview
additional information
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molecular homology modeling with CfGGPPS as model sequence and PDB entries 2E8V and 2Q80 (yeast and human GGPPSs) as templates, ligand binding analysis, overview
additional information
the enzyme supplies geranylgeranyl diphosphate or the production of carotenoids and other groups of plastidial isoprenoids
additional information
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the enzyme supplies geranylgeranyl diphosphate or the production of carotenoids and other groups of plastidial isoprenoids