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Information on EC 2.5.1.29 - geranylgeranyl diphosphate synthase and Organism(s) Homo sapiens and UniProt Accession O95749
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2.5.1.29 geranylgeranyl diphosphate synthaseIUBMB Comments
Some forms of this enzyme will also use geranyl diphosphate and dimethylallyl diphosphate as donors; it will not use larger prenyl diphosphates as efficient donors.
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Word Map
- 2.5.1.29
-
geranylgeranylation
-
isoprenoids
-
carotenoid
- bisphosphonates
-
prenylation
- mevalonate
-
dimethylallyl
- phytoene
- prenyltransferases
-
diterpene
-
allyl
-
diterpenoids
-
isoprenylation
- lycopene
- taxus
- uredovora
-
aspartate-rich
- synthesis
-
kaurene
- drug development
- diagnostics
- fujikuroi
- taxadiene
- medicine
- agriculture
- pharmacology
- nutrition
-
20-carbon
-
dmapp
-
carotenogenesis
-
carotenogenic
- biotechnology
-
copalyl
- food industry
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
geranylgeranyl diphosphate synthase, ggpp synthase, ggdps, ggps1, ggpps1, cotb1, tgfpps, geranylgeranyl diphosphate synthase 1, geranylgeranyl pyrophosphate synthetase, ggppase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
farnesyltransferase
-
-
-
-
geranylgeranyl diphosphate synthase
-
-
-
-
geranylgeranyl pyrophosphate synthase
geranylgeranyl pyrophosphate synthetase
-
-
-
-
geranylgeranyl-PP synthetase
-
-
-
-
synthetase, geranylgeranyl pyrophosphate
-
-
-
-
geranylgeranyl pyrophosphate synthase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
alkenyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(2E,6E)-farnesyl-diphosphate:isopentenyl-diphosphate farnesyltranstransferase
Some forms of this enzyme will also use geranyl diphosphate and dimethylallyl diphosphate as donors; it will not use larger prenyl diphosphates as efficient donors.
CAS REGISTRY NUMBER
COMMENTARY
9032-58-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
-
-
?
geranyl diphosphate + 3-desmethylisopentenyl diphosphate
diphosphate + 3-desmethylfarnesyl diphosphate
i.e. but-3-enyl diphosphate
-
-
?
geranyl diphosphate + 3-ethylbut-3-enyl diphosphate
diphosphate + 3-ethylfarnesyl diphosphate
-
-
-
?
geranyl diphosphate + 3-propylbut-3-enyl diphosphate
diphosphate + 3-propylfarnesyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
-
-
-
?
(E,E)-farnesyl diphosphate + isopentenyl diphosphate
geranylgeranyl diphosphate + diphosphate
-
-
-
?
geranyl diphosphate + 2 isopentenyl diphosphate
geranylgeranyl diphosphate + 2 diphosphate
-
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
-
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
the enzyme participates in the mevalonate pathway, overview, enzyme inhibition leads to enhanced depletion of intracellular geranylgeranyl diphosphate relative to the nitrogenous bisphosphonate, overview
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
the enzyme takes part in the mevalonate pathway of isoprenoid synthesis, and plays a crucial role in cell survival, overview
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
tight binding substrate and product structures, overview
-
-
?
additional information
?
-
enzyme geranylgeranyl diphosphate synthase catalyzes the sequential condensation of isopentenyl diphosphates with the allylic substrates dimethylallyl diphosphate (DMAPP), geranyl diphosphate (GPP), or both to produce geranylgeranyl diphosphate (GGPP)
-
-
?
additional information
?
-
enzyme substrate specificity in reactions using 3-alkyl analogues of isopentenyl diphosphate as substrate, overview. No activity with 3-butylbut-3-enyl diphosphate
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
-
-
-
?
(E,E)-farnesyl diphosphate + isopentenyl diphosphate
geranylgeranyl diphosphate + diphosphate
-
-
-
-
?
geranyl diphosphate + 2 isopentenyl diphosphate
geranylgeranyl diphosphate + 2 diphosphate
-
-
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
additional information
?
-
enzyme geranylgeranyl diphosphate synthase catalyzes the sequential condensation of isopentenyl diphosphates with the allylic substrates dimethylallyl diphosphate (DMAPP), geranyl diphosphate (GPP), or both to produce geranylgeranyl diphosphate (GGPP)
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
the enzyme participates in the mevalonate pathway, overview, enzyme inhibition leads to enhanced depletion of intracellular geranylgeranyl diphosphate relative to the nitrogenous bisphosphonate, overview
-
-
?
trans,trans-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + geranylgeranyl diphosphate
-
the enzyme takes part in the mevalonate pathway of isoprenoid synthesis, and plays a crucial role in cell survival, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
Mg2+
bisphosphonate binding depends on coordination by Mg2+. Three Mg2+ ions are involved in bisphosphonate-protein interactions. Mg2+ ions are vital for drug binding and provide a structural basis for future computational design of geranylgeranyl diphosphate inhibitors
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
((((6E,11E)-9-((((S)-3,7-dimethyloct-6-en-1-yl)oxy)((pivaloyloxy)methoxy)phosphoryl)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraen-9-yl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
-
((((E)-1((((S)-3,7-dimethyloct-6-en-1-yl)oxy)((pialoxy)methoxy)phosphoryl)-4,8-dimethylnona-3,7-dien-1-yl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
-
((((E)-2-((((R)-3,7-dimethyloct-6-en-1-yl)oxy)((pivaloyloxy)methoxy)phosphoryl)-5,9-dimethyldeca-4,8-dien-2-yl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
-
((((E)-2-((((S)-3,7-dimethyloct-6-en-1-yl)oxy)((pivaloyloxy)methoxy)phosphoryl)-5,9-dimethyldeca-4,8-dien-2-yl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
-
((((E)-4-((((S)-3,7-dimethyloct-6-en-1-yl)oxy)((pivaloyloxy)methoxy)phosphoryl)-7,11-dimethyldodeca-1,6,10-trien-4-yl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
-
((((E)-5-((((S)-3,7-dimethyloct-6-en-1-yl)oxy)((pivaloyloxy)methoxy)phosphoryl)-2,8,12-trimethyltrideca-2,7,11-trien-5-yl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
-
(((2-(3-((3-fluoro-4-methoxyphenyl)carbamoyl)phenyl)-thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis-(phosphonic acid)
-
(((2-(3-((4-methoxyphenyl)carbamoyl)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
-
(((2-(3-(4-fluorobenzamido)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
-
-
(((2-(3-(4-methoxybenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
-
(((2-(3-(4-methylbenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
-
(((2-(3-(phenylcarbamoyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
-
(((2-(3-benzamidophenyl)thieno[2,3-d]pyrimidin-4-yl)-amino)methylene)bis(phosphonic acid)
-
(2-[1-[(3E)-4,8-dimethylnona-3,7-dien-1-yl]-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl)bis(phosphonic acid)
identification of a potent triazole bisphosphonate inhibitor of geranylgeranyl diphosphate synthase with very good selectivity for this enzyme over farnesyl diphosphate synthase. This compound also potently disrupts geranylgeranylation and induces cytotoxicity in human myeloma cells at submicromolar levels, suggesting that it may serve as a lead compound for treatment of malignancies characterized by excessive protein secretion
(3S)-3,7-dimethyloct-6-en-1-yl trimethyl [(6E)-2,6-dimethyldeca-2,6-diene-9,9-diyl]bis(phosphonate)
-
(4aR,10aS)-4a-[5-(4-bromophenyl)-1,3,4-oxadiazol-2-yl]-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-2,3,4,4a,10,10a-hexahydrophenanthren-9(1H)-one
-
(4aR,10aS)-4a-[5-[(1R)-1-aminoethyl]-1,3,4-oxadiazol-2-yl]-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-2,3,4,4a,10,10a-hexahydrophenanthren-9(1H)-one
-
(4bR,8aS)-4b-(5-acetyl-1,3,4-oxadiazol-2-yl)-8,8-dimethyl-2-(propan-2-yl)-5,6,7,8,8a,9-hexahydrophenanthrene-3,4,10(4bH)-trione
-
(4bR,8aS)-4b-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8,8-dimethyl-2-(propan-2-yl)-5,6,7,8,8a,9-hexahydrophenanthrene-3,4,10(4bH)-trione
-
(4bR,8aS)-4b-(5-[(1S)-1-[(hydroxymethyl)amino]ethyl]-1,3,4-oxadiazol-2-yl)-8,8-dimethyl-2-(propan-2-yl)-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-3,4-diol
-
(R)-3,7-dimethyloct-6-en-1-yl methyl ((E)-1-(dimethoxyphosphoryl)-4,8-dimethylnona-3,7-dien-1-yl)phosphonate
-
(R)-3,7-dimethyloct-6-en-1-yl methyl ((E)-2-(dimethoxyphosphoryl)-5,9-dimethyldeca-4,8-dien-2-yl)phosphonate
-
(R)-3,7-dimethyloct-6-en-1-yl methyl ((E)-4,8-dimethylnona-3,7-dien-1-yl)phosphonate
-
(S)-3,7-dimethyloct-6-en-1-yl methyl ((6E,11E)-9-(dimethoxyphosphoryl)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraen-9-yl)phosphonate
-
(S)-3,7-dimethyloct-6-en-1-yl methyl ((E)-1-(dimethoxyphosphoryl)-4,8-dimethylnona-3,7-dien-1-yl)phosphonate
-
(S)-3,7-dimethyloct-6-en-1-yl methyl ((E)-4,8-dimethylnona-3,7-dien-1-yl)phosphonate
-
(S)-3,7-dimethyloct-6-en-1-yl methyl ((E)-4-(dimethoxyphosphoryl)-7,11-dimethyldodeca-1,6,10-trien-4-yl)phosphonate
-
(S)-3,7-dimethyloct-6-en-1-yl methyl ((E)-5-(dimethoxyphosphoryl)-2,8,12-trimethyltrideca-2,7,11-trien-5-yl)phosphonate
-
2-[11,12-dihydroxy-20-oxoabieta-8(14),9(11),12-trien-20-yl]hydrazine-1-carboxamide
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-(5-methylhex-4-enamido)propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(2E)-3,7-dimethylocta-2,6-dienamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(2Z)-3,7-dimethylocta-2,6-dienamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(3R)-3,7-dimethyloct-6-enamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(3S)-3,7-dimethyloct-6-enamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(3Z)-4,8-dimethylnona-3,7-dienamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(4E)-5,9-dimethyldeca-4,8-dienamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(4Z)-5,9-dimethyldeca-4,8-dienamido]propyl)phosphonate
-
disodium (1-[bis(sodiooxy)phosphoryl]-3-[3,7-dimethylocta-2,6-dienamido]propyl)phosphonate
-
methyl 11,12-dihydroxy-7-(phenylsulfanyl)abieta-8(14),9(11),12-trien-20-oate
-
methyl 7-[(2-hydroxyethyl)sulfanyl]-11,12-dioxoabieta-8,13-dien-20-oate
-
N-acetyl-S-((4aR,10aS)-5,6-dihydroxy-7-isopropyl-4a-(methoxycarbonyl)-1,1-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-9-yl)-L-cysteine
-
tert-butyl [(1S)-1-[5-[(4aR,10aS)-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-1,3,4,9,10,10a-hexahydrophenanthren-4a(2H)-yl]-1,3,4-oxadiazol-2-yl]ethyl]carbamate
-
[(6E)-2,6-dimethyl-10-[1-(4-methylpent-3-en-1-yl)-1H-1,2,3-triazol-4-yl]deca-2,6-diene-9,9-diyl]bis(phosphonic acid)
-
[(6E,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyl]bis(phosphonic acid)
-
[([6-[4-(trifluoromethyl)phenyl]thieno[2,3-d]pyrimidin-4-yl]amino)methylene]bis(phosphonic acid)
-
[2-[1-(4-methylpent-3-en-1-yl)-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
[[(2-phenylthieno[2,3-d]pyrimidin-4-yl)amino]methylene]bis(phosphonic acid)
-
[[(5,6-dihydrothieno[2,3-d]pyrimidin-4-yl)amino]methylene]bis(phosphonic acid)
-
[[(6-phenylthieno[2,3-d]pyrimidin-4-yl)amino]methylene]bis(phosphonic acid)
-
(2-[1-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl)bis(phosphonic acid)
-
a mixture of olefin isomers
(2E,6E)-farnesyl-bis(phosphonic acid)
-
both inhibition of in vitro reaction as well as of cellular geranylgeranylation
(2E,6E)-farnesyl-geranyl-bis(phosphonic acid)
-
both inhibition of in vitro reaction as well as of cellular geranylgeranylation
(2E,6Z)-farnesyl-bis(phosphonic acid)
-
both inhibition of in vitro reaction as well as of cellular geranylgeranylation
(6Z,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyldiphosphonate
-
-
(6Z,11Z)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyldiphosphonate
-
-
(E)-(2-(1-((3-methyl-3-(4-methylpent-3-en-1-yl)oxiran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
-
-
(E)-(2-(1-(3,7-dimethylocta-2,6-dien-1-yl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
-
-
(Z)-(2-(1-((3-methyl-3-(4-methylpent-3-en-1-yl)oxiran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)digeranyl bisphosphonate
-
cell treatment with inhibitor DGBP results in the accumulation of unmodified Rap1a and Rab6
(Z)-(2-(1-(3,7-dimethylocta-2,6-dien-1-yl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
-
-
4-[(5-[[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl]-1H-imidazol-1-yl)methyl]benzonitrile
-
a dual prenyl transferase inhibitor that has advanced to clinical trials
bis[(6E)-2,6-dimethylnona-2,6-diene-9,9-diyl]bis(phosphonic acid)
-
both inhibition of in vitro reaction as well as of cellular geranylgeranylation
N-([5-[(1H-imidazol-4-ylmethyl)amino]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine
-
-
[(6E,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyl]bis(phosphonic acid)
-
-
[1-hydroxy-2-(1,1':4',1''-terphenyl-3-yl)ethane-1,1-diyl]bis(phosphonic acid)
-
-
digeranyl bisphosphonate
-
inhibition of geranylgeranyl diphosphate synthase induces apoptosis through multiple mechanisms and displays synergy with inhibition of other isoprenoid biosynthetic enzymes
additional information
pivaloyloxymethyl prodrugs of several compounds based on a motif , prepared with one isoprenoid chain on the alpha-carbon, a second included as a phosphonate ester, and the potential for a third at the alpha-carbon, are prepared and the resulting compounds are tested for their ability to disrupt protein geranylgeranylation and induce cytotoxicity in myeloma cells. The enzyme GGDPS inhibition demonstrate a structurefunction relationship which is dependent on the nature of the alkyl group at the alpha-carbon. Cytotoxicity of the compounds in myeloma cells, overview
-
additional information
geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma
-
additional information
-
geranylgeranyl diphosphate synthase is inhibited by a variety of bisphosphonates
-
additional information
-
potency and specificity of bisphosphonate enzyme inhibitors
-
additional information
-
GGDPS inhibitors versus geranylgeranyl transferase inhibitors in cancer therapy, overview. The use of GGDPS inhibitors, thereby blocking prenylation of both sets of geranylgeranylated proteins, may be more effective than targeting either set alone through the use of a geranylgeranyl transferase I inhibitor or a geranylgeranyl transferase II inhibitor (such as the phosphonocarboxylate 3-PEHPC)
-
additional information
-
statins inhibit the enzyme indirectly through feedback inhibition via inhibition of the first and rate-limiting step of isoprenoid biosynthesis, namely, conversion of HMG-CoA to mevalonate by HMG-CoA reductase. Geranylgeranyl diphosphate depletion (and consequently geranylgeranylation) is strongly linked to statin-induced apoptosis in several models. In endothelial cells, statins potentiate tumor necrosis factor-alpha-mediated apoptosis by blocking rhoA geranylgeranylation
-
additional information
-
evaluation of geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase, overview. Stereoselective synthesis of these triazoles through the use of epoxy azides for the cycloaddition reaction followed by regeneration of the desired olefin, a Z-olefin isomer is a potent and selective inhibitor of geranylgeranyl diphosphate synthase
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
steady-state kinetics, recombinant enzyme
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.025
geranylgeranyl diphosphate
-
pH 7.7, 37°C, recombinant enzyme, versus trans,trans-farnesyl diphosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.086
(((2-(3-((3-fluoro-4-methoxyphenyl)carbamoyl)phenyl)-thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis-(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
75
(((2-(3-((4-methoxyphenyl)carbamoyl)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
0.042
(((2-(3-(4-fluorobenzamido)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
-
0.085
(((2-(3-(4-methoxybenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
0.1
(((2-(3-(4-methylbenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
0.049
(((2-(3-(phenylcarbamoyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
0.064
(((2-(3-benzamidophenyl)thieno[2,3-d]pyrimidin-4-yl)-amino)methylene)bis(phosphonic acid)
0.000045
(2-[1-[(3E)-4,8-dimethylnona-3,7-dien-1-yl]-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication
0.04
(4aR,10aS)-4a-[5-(4-bromophenyl)-1,3,4-oxadiazol-2-yl]-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-2,3,4,4a,10,10a-hexahydrophenanthren-9(1H)-one
Homo sapiens
pH 7.5, 23°C
0.0494
(4aR,10aS)-4a-[5-[(1R)-1-aminoethyl]-1,3,4-oxadiazol-2-yl]-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-2,3,4,4a,10,10a-hexahydrophenanthren-9(1H)-one
Homo sapiens
pH 7.5, 23°C
0.0123
(4bR,8aS)-4b-(5-acetyl-1,3,4-oxadiazol-2-yl)-8,8-dimethyl-2-(propan-2-yl)-5,6,7,8,8a,9-hexahydrophenanthrene-3,4,10(4bH)-trione
Homo sapiens
pH 7.5, 23°C
0.0109
(4bR,8aS)-4b-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8,8-dimethyl-2-(propan-2-yl)-5,6,7,8,8a,9-hexahydrophenanthrene-3,4,10(4bH)-trione
Homo sapiens
pH 7.5, 23°C
0.0432
(4bR,8aS)-4b-(5-[(1S)-1-[(hydroxymethyl)amino]ethyl]-1,3,4-oxadiazol-2-yl)-8,8-dimethyl-2-(propan-2-yl)-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-3,4-diol
Homo sapiens
pH 7.5, 23°C
0.0147
12-hydroxy-11,20-epoxyabieta-8(14),9(11),12-trien-20-one
Homo sapiens
pH 7.5, 23°C
0.0379
2-[11,12-dihydroxy-20-oxoabieta-8(14),9(11),12-trien-20-yl]hydrazine-1-carboxamide
Homo sapiens
pH 7.5, 23°C
0.0144
disodium (1-[bis(sodiooxy)phosphoryl]-3-(5-methylhex-4-enamido)propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0047
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(2E)-3,7-dimethylocta-2,6-dienamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0377
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(2Z)-3,7-dimethylocta-2,6-dienamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0034
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(3R)-3,7-dimethyloct-6-enamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0054
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(3S)-3,7-dimethyloct-6-enamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0037
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(3Z)-4,8-dimethylnona-3,7-dienamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0008
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(4E)-5,9-dimethyldeca-4,8-dienamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0011
disodium (1-[bis(sodiooxy)phosphoryl]-3-[(4Z)-5,9-dimethyldeca-4,8-dienamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0024
disodium (1-[bis(sodiooxy)phosphoryl]-3-[3,7-dimethylocta-2,6-dienamido]propyl)phosphonate
Homo sapiens
pH and temperature not specified in the publication
0.0055
methyl 11,12-dihydroxy-7-(phenylsulfanyl)abieta-8(14),9(11),12-trien-20-oate
Homo sapiens
pH 7.5, 23°C
0.0354
methyl 11,12-dihydroxy-7-methoxyabieta-8(14),9(11),12-trien-20-oate
Homo sapiens
pH 7.5, 23°C
0.0436
methyl 11,12-dihydroxy-7-oxoabieta-8(14),9(11),12-trien-20-oate
Homo sapiens
pH 7.5, 23°C
0.0152
methyl 11,12-dihydroxyabieta-8(14),9(11),12-trien-20-oate
Homo sapiens
pH 7.5, 23°C
0.0459
methyl 7-[(2-hydroxyethyl)sulfanyl]-11,12-dioxoabieta-8,13-dien-20-oate
Homo sapiens
pH 7.5, 23°C
0.0154
N-acetyl-S-((4aR,10aS)-5,6-dihydroxy-7-isopropyl-4a-(methoxycarbonyl)-1,1-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-9-yl)-L-cysteine
Homo sapiens
pH 7.5, 23°C
0.0378
N-benzyl-11,12-dihydroxyabieta-8(14),9(11),12-trien-20-amide
Homo sapiens
pH 7.5, 23°C
0.0347
N-cycloheptyl-11,12-dihydroxyabieta-8(14),9(11),12-trien-20-amide
Homo sapiens
pH 7.5, 23°C
0.0375
tert-butyl [(1S)-1-[5-[(4aR,10aS)-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-1,3,4,9,10,10a-hexahydrophenanthren-4a(2H)-yl]-1,3,4-oxadiazol-2-yl]ethyl]carbamate
Homo sapiens
pH 7.5, 23°C
0.00038
[(6E)-2,6-dimethyl-10-[1-(4-methylpent-3-en-1-yl)-1H-1,2,3-triazol-4-yl]deca-2,6-diene-9,9-diyl]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication
0.43
[(6E,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyl]bis(phosphonic acid)
1.5
[([6-[4-(trifluoromethyl)phenyl]thieno[2,3-d]pyrimidin-4-yl]amino)methylene]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.00043
[2-[1-(4-methylpent-3-en-1-yl)-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication
0.082
[[(2-phenylthieno[2,3-d]pyrimidin-4-yl)amino]methylene]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.094
[[(6-phenylthieno[2,3-d]pyrimidin-4-yl)amino]methylene]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.0022
(2-[1-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-1H-1,2,3-triazol-4-yl]ethane-1,1-diyl)bis(phosphonic acid)
Homo sapiens
-
pH 7.7, 22°C
0.0006
(3E,7Z)-4,8,12-trimethyl-1-phosphonitotrideca-3,7,11-trienylphosphonate
Homo sapiens
-
-
0.04
(3Z,7E)-4,8,12-trimethyl-1-phosphonitotrideca-3,7,11-trienylphosphonate
Homo sapiens
-
-
0.07
(3Z,7Z)-4,8,12-trimethyl-1-phosphonitotrideca-3,7,11-trienylphosphonate
Homo sapiens
-
-
0.006
(6Z,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyldiphosphonate
Homo sapiens
-
-
0.003
(6Z,11Z)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyldiphosphonate
Homo sapiens
-
-
0.023
(E)-(2-(1-((3-methyl-3-(4-methylpent-3-en-1-yl)oxiran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
Homo sapiens
-
pH 7.7, 22°C
0.017
(E)-(2-(1-(3,7-dimethylocta-2,6-dien-1-yl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
Homo sapiens
-
pH 7.7, 22°C
0.017
(Z)-(2-(1-((3-methyl-3-(4-methylpent-3-en-1-yl)oxiran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)digeranyl bisphosphonate
Homo sapiens
-
pH 7.7, 22°C
0.00038
(Z)-(2-(1-(3,7-dimethylocta-2,6-dien-1-yl)-1H-1,2,3-triazol-4-yl)ethane-1,1-diyl)bis(phosphonate)
Homo sapiens
-
pH 7.7, 22°C
0.0002
bis[(6E)-2,6-dimethylnona-2,6-diene-9,9-diyl]bis(phosphonic acid)
Homo sapiens
-
pH 7.5, 37°C
75
(((2-(3-((4-methoxyphenyl)carbamoyl)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, mutant enzyme Y246D
75
(((2-(3-((4-methoxyphenyl)carbamoyl)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.085
(((2-(3-(4-methoxybenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, mutant enzyme Y246D
0.085
(((2-(3-(4-methoxybenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.1
(((2-(3-(4-methylbenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, mutant enzyme Y246D
0.1
(((2-(3-(4-methylbenzamido)phenyl)thieno[2,3-d]-pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.049
(((2-(3-(phenylcarbamoyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, mutant enzyme Y246D
0.049
(((2-(3-(phenylcarbamoyl)phenyl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.064
(((2-(3-benzamidophenyl)thieno[2,3-d]pyrimidin-4-yl)-amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, mutant enzyme Y246D
0.064
(((2-(3-benzamidophenyl)thieno[2,3-d]pyrimidin-4-yl)-amino)methylene)bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
0.43
[(6E,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyl]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, mutant enzyme Y246D
0.43
[(6E,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyl]bis(phosphonic acid)
Homo sapiens
pH and temperature not specified in the publication, wild-type enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
the enzyme is a target for treating bone resorption diseases and some cancers
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
physiological function
-
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
additional information
enzyme-substrate docking using the crystal structure of human GGPPase, PDB ID 2Q80PDB
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). GGPPS_HUMAN
300
0
34871
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
-
three dimers join together to form a propeller-bladed hexameric molecule, quaternary structure, overview
octamer
-
the active form of GGPS in the solution is an octamer (comprising of four dimers) rather than hexamer or dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
-
proteins modified post-translationally by geranylgeranylation have been 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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop method. Structures of a series of n-alkyl and dialkenyl bisphosphonates bound to GGPPS. The binding modes seen crystallographically can be well predicted computationally, facilitating the development of quantitative structure-activity models
sitting drop vapor diffusion method at 19°C. 2.2 A crystal structure of hGGPPS in complex with ibandronate
native protein, 20°C, sitting drop vapour diffusion mthod, mixing of 200 nl of 90 mg/ml protein in 10 mM HEPES, pH 7.5, 500 mM NaCl, 5% glycerol with 100 nl of precipitant solution consisting of 25% PEG 3350, 200 mM magnesium formate, pH 5.5, and equilibration against 0.1 ml of the precipitant solution, selenomethionine-labeled protein by suspending a 0.003 ml drop containing 26 mg/ml protein, 333 mM NaCl, 0.67 mM MgCl2, 0.67 mM GGPP, 3% glycerol, 15% 2-methyl-2,4-pentanediol, 1.7% PEG 10,000, 6.7 mM HEPES, pH 7.5, over a 1 ml reservoir containing 45% 2-methyl-2,4-pentanediol, and 5% PEG 10000, X-ray diffraction structure determination and analysis at 2.7-2.8 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
women with 2 deletion alleles of GGPS1 -8188A ins/del (rs3840452) have significantly higher femoral neck bone marrow densitiy at baseline compared with those with one or no deletion allele. The response rate of women with 2 deletion alleles of GGPS1 -8188A ins/del (28.6%) is significantly lower than the rate of women with one or no deletion allele. Women with 2 deletion alleles of GGPS1 -8188A ins/del have 7fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188. Other polymorphisms in or GGPS1 are not associated with lumbar spine bone marrow density or femoral neck bon marrow density
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged enzyme from Escherichia coli, the His-tag is cleaved of by TEV
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues
overexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
overexpression of geranylgeranyl diphosphate synthase correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating epithelial-mesenchymal transition
medicine
enzyme expression is significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of geranylgeranyl diphosphate synthase is correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients
pharmacology
drug development
-
validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism
medicine
pharmacology
geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma
pharmacology
the enzyme is a valuable therapeutic target in oncology and more specifically for the treatment of multiple myeloma
medicine
-
women with 2 deletion alleles of GGPS1 -8188A ins/del (rs3840452) have significantly higher femoral neck bone marrow densitiy at baseline compared with those with one or no deletion allele. The response rate of women with 2 deletion alleles of GGPS1 -8188A ins/del (28.6%) is significantly lower than the rate of women with one or no deletion allele. Women with 2 deletion alleles of GGPS1 -8188A ins/del have 7fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188. Other polymorphisms in or GGPS1 are not associated with lumbar spine bone marrow density or femoral neck bon marrow density
medicine
-
validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Szabo, C.M.; Matsumura, Y.; Fukura, S.; Martin, M.B.; Sanders, J.M.; Sengupta, S.; Cieslak, J.A.; Loftus, T.C.; Lea, C.R.; Lee, H.J.; Koohang, A.; Coates, R.M.; Sagami, H.; Oldfield, E.
Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents
J. Med. Chem.
45
2185-2196
2002
Homo sapiens
Wiemer, A.J.; Tong, H.; Swanson, K.M.; Hohl, R.J.
Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase
Biochem. Biophys. Res. Commun.
353
921-925
2007
Homo sapiens
Kavanagh, K.L.; Dunford, J.E.; Bunkoczi, G.; Russell, R.G.; Oppermann, U.
The crystal structure of human geranylgeranyl pyrophosphate synthase reveals a novel hexameric arrangement and inhibitory product binding
J. Biol. Chem.
281
22004-22012
2006
Homo sapiens
Wiemer, A.J.; Yu, J.S.; Lamb, K.M.; Hohl, R.J.; Wiemer, D.F.
Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors
Bioorg. Med. Chem.
16
390-399
2008
Homo sapiens
Miyagi, Y.; Matsumura, Y.; Sagami, H.
Human geranylgeranyl diphosphate synthase is an octamer in solution
J. Biochem.
142
377-381
2007
Homo sapiens
K-M Chen, C.; Hudock, M.P.; Zhang, Y.; Guo, R.T.; Cao, R.; No, J.H.; Liang, P.H.; Ko, T.P.; Chang, T.H.; Chang, S.C.; Song, Y.; Axelson, J.; Kumar, A.; Wang, A.H.; Oldfield, E.
Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation
J. Med. Chem.
51
5594-5607
2008
Homo sapiens (O95749)
Dudakovic, A.; Wiemer, A.J.; Lamb, K.M.; Vonnahme, L.A.; Dietz, S.E.; Hohl, R.J.
Inhibition of geranylgeranyl diphosphate synthase induces apoptosis through multiple mechanisms and displays synergy with inhibition of other isoprenoid biosynthetic enzymes
J. Pharmacol. Exp. Ther.
324
1028-1036
2008
Homo sapiens
Choi, H.J.; Choi, J.Y.; Cho, S.W.; Kang, D.; Han, K.O.; Kim, S.W.; Kim, S.Y.; Chung, Y.S.; Shin, C.S.
Genetic polymorphism of geranylgeranyl diphosphate synthase (GGSP1) predicts bone density response to bisphosphonate therapy in Korean women
Yonsei Med. J.
51
231-238
2010
Homo sapiens
Wiemer, A.J.; Wiemer, D.F.; Hohl, R.J.
Geranylgeranyl diphosphate synthase: an emerging therapeutic target
Clin. Pharmacol. Ther.
90
804-812
2011
Homo sapiens
Wills, V.S.; Allen, C.; Holstein, S.A.; Wiemer, D.F.
Potent triazole bisphosphonate inhibitor of geranylgeranyl diphosphate synthase
ACS Med. Chem. Lett.
6
1195-1198
2015
Homo sapiens (O95749), Homo sapiens
Zhou, X.; Ferree, S.D.; Wills, V.S.; Born, E.J.; Tong, H.; Wiemer, D.F.; Holstein, S.A.
Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase
Bioorg. Med. Chem.
22
2791-2798
2014
Homo sapiens
Foust, B.J.; Allen, C.; Holstein, S.A.; Wiemer, D.F.
A new motif for inhibitors of geranylgeranyl diphosphate synthase
Bioorg. Med. Chem.
24
3734-3741
2016
Homo sapiens (O95749)
Ohya, N.; Ichijo, T.; Sato, H.; Nakamura, T.; Yokota, S.; Sagami, H.; Nagaki, M.
Specificity of geranylgeranyl diphosphate synthase for homoallylic substrate analogs
J. Mol. Catal. B
120
179-182
2015
Homo sapiens (O95749)
-
Goetz, D.B.; Varney, M.L.; Wiemer, D.F.; Holstein, S.A.
Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors
Bioorg. Med. Chem.
28
115604
2020
Homo sapiens (O95749)
Wang, X.; Xu, W.; Zhan, P.; Xu, T.; Jin, J.; Miu, Y.; Zhou, Z.; Zhu, Q.; Wan, B.; Xi, G.; Ye, L.; Liu, Y.; Gao, J.; Li, H.; Lv, T.; Song, Y.
Overexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma
J. Cell. Mol. Med.
22
2177-2189
2018
Homo sapiens (O95749), Homo sapiens
Lacbay, C.M.; Waller, D.D.; Park, J.; Gomez Palou, M.; Vincent, F.; Huang, X.F.; Ta, V.; Berghuis, A.M.; Sebag, M.; Tsantrizos, Y.S.
Unraveling the prenylation-cancer paradox in multiple myeloma with novel geranylgeranyl pyrophosphate synthase (GGPPS) inhibitors
J. Med. Chem.
61
6904-6917
2018
Homo sapiens (O95749)
Han, S.; Li, X.; Xia, Y.; Yu, Z.; Cai, N.; Malwal, S.R.; Han, X.; Oldfield, E.; Zhang, Y.
Farnesyl pyrophosphate synthase as a target for drug development discovery of natural-product-derived inhibitors and their activity in pancreatic cancer cells
J. Med. Chem.
62
10867-10896
2019
Homo sapiens (O95749)
Lisnyansky, M.; Yariv, E.; Segal, O.; Marom, M.; Loewenstein, A.; Ben-Tal, N.; Giladi, M.; Haitin, Y.
Metal coordination is crucial for geranylgeranyl diphosphate synthase-bisphosphonate interactions a crystallographic and computational analysis
Mol. Pharmacol.
96
580-588
2019
Homo sapiens (O95749), Homo sapiens
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