Information on EC 2.5.1.10 - (2E,6E)-farnesyl diphosphate synthase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.5.1.10
-
RECOMMENDED NAME
GeneOntology No.
(2E,6E)-farnesyl diphosphate synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
bimolecular nucleophilic substitution, SN2 reaction, proceeds with an inversion of configuration at the diphosphate-bearing carbon of the allylic substrate and removal of the pro-R hydrogen from the C-2 of isopentenyl diphosphate in these trans-polyprenol synthetic reactions
-
geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
alkenyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
all-trans-farnesol biosynthesis
-
Biosynthesis of secondary metabolites
-
bisabolene biosynthesis
-
Metabolic pathways
-
Terpenoid backbone biosynthesis
-
trans, trans-farnesyl diphosphate biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
geranyl-diphosphate:isopentenyl-diphosphate geranyltranstransferase
Some forms of this enzyme will also use dimethylallyl diphosphate as a substrate. The enzyme will not accept larger prenyl diphosphates as efficient donors.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E-farnesyl diphosphate synthase
Q08291
-
E-farnesyl diphosphate synthase
Geobacillus stearothermophilus ATCC 10149
Q08291
-
-
E-FPP synthase
Q08291
-
E-FPP synthase
Geobacillus stearothermophilus ATCC 10149
Q08291
-
-
ERG20
P08524
gene name
farnesyl diphosphate synthase
-
-
farnesyl diphosphate synthase
-
-
farnesyl diphosphate synthase
P08524
-
farnesyl diphosphate synthase
-
-
farnesyl diphosphate synthase
Q197X6
-
farnesyl diphosphate synthase
Q197X6
Toxoplasma gondii possesses a bifunctional farnesyl diphosphate/geranylgeranyl diphosphate synthase
farnesyl diphosphate synthase
Q197X6
Toxoplasma gondii possesses a bifunctional farnesyl diphosphate/geranylgeranyl diphosphate synthase
-
farnesyl diphosphate synthase
-
-
farnesyl diphosphate synthase 1
G0YZR3
-
farnesyl diphosphate synthase 2
G0YZR4
-
farnesyl pyrophosphate synthase
B8XPY7
-
farnesyl pyrophosphate synthase
P14324
-
farnesyl pyrophosphate synthetase
-
-
-
-
farnesyl-diphosphate synthase
-
-
-
-
farnesyl-diphosphate synthase
Q42698
-
farnesylpyrophosphate synthetase
-
-
-
-
FPP synthase
B8XPY7
-
FPPS
P14324
-
FPPS
Q197X6
-
-
FPPS1
G0YZR3
isoform
FPPS2
G0YZR4
isoform
geranyl transferase I
-
-
-
-
geranyltranstransferase
-
-
-
-
omega,E,E-farnesyl diphosphate synthase
-
-
prenyltransferase
-
-
-
-
type I farnesyl diphosphate synthase
-
-
CAS REGISTRY NUMBER
COMMENTARY
37277-79-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
grand fir
-
-
Manually annotated by BRENDA team
dual geranyl/farnesyl diphosphate synthase
UniProt
Manually annotated by BRENDA team
Madagascar periwinkle
SwissProt
Manually annotated by BRENDA team
wintersweet
SwissProt
Manually annotated by BRENDA team
bifunctional geranyl diphosphate synthase EC 2.5.1.1 and farnesyl diphosphate synthase EC 2.5.1.10
-
-
Manually annotated by BRENDA team
Geobacillus stearothermophilus ATCC 10149
-
UniProt
Manually annotated by BRENDA team
dual geranyl/farnesyl diphosphate synthase
UniProt
Manually annotated by BRENDA team
enzyme catalyzes reactions of EC 2.5.1.1, and EC 2.5.1.10. Isoforms IPPS1-L and IPPS1-S are identical except for an N-terminal extension of 32 amino acids
-
-
Manually annotated by BRENDA team
Pumpkin
-
-
-
Manually annotated by BRENDA team
isoform FPPS1; bird cherry-oat aphid
UniProt
Manually annotated by BRENDA team
isoform FPPS2; bird cherry-oat aphid
UniProt
Manually annotated by BRENDA team
isoenzyme I and II
-
-
Manually annotated by BRENDA team
bifunctional geranyl diphosphate synthase EC 2.5.1.1 and farnesyl diphosphate synthase EC 2.5.1.10
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
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
-
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
B8XPY7, -
the enzyme regulates the volatile sesquiterpenes in wintersweet flower
physiological function
-
the enzyme is involved in the biosynthesis of the monoterpenoid precursors needed for formation of the defensive compound chrysomelidial
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(E)-ethynyldimethylallyl diphosphate + isopentenyl diphosphate
(E)-ethynylfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
double condensation product. Yield is 0.8% E-ethynylfarnesyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate
-
?
(Z)-ethynyldimethylallyl diphosphate + isopentenyl diphosphate
(Z)-ethynylfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
sole product with wild-type, yield is 21.9% Z-ethynylfarnesyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate
-
-
(Z)-ethynyldimethylallyl diphosphate + isopentenyl diphosphate
(Z)-ethynylfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
sole product with wild-type, yield is 88.8% Z-ethynylfarnesyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate. Mutant Y81D yields products ethynylgeranyl, ethynylfarnesyl, and ethynylgeranylgeranyl diphosphates
-
-
8-acetoxygeranyl diphosphate + isopentenyl diphosphate
diphosphate + 12-acetoxyfarnesyl diphosphate
show the reaction diagram
Geobacillus stearothermophilus, Geobacillus stearothermophilus ATCC 10149
Q08291
-
21.8% yield
-
?
8-hydroxygeranyl diphosphate + isopentenyl diphosphate
hydroxyfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
mutants Y81S and Y81D, produce additionally hydroxygeranylgeranyl diphosphate plus a small amount of hydroxygeranylfarnesyl diphosphate
-
?
8-methoxygeranyl diphosphate + isopentenyl diphosphate
methoxyfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
mutants Y81S and Y81D, produce methoxygeranylgeranyl diphosphate as main product plus some methoxyfarnesyl diphosphate
-
?
cyclohexylideneethyl diphosphate + 2-cyclohexenylethyl diphosphate
(cyclohexylideneethyl)-cyclohexylideneethyl diphosphate
show the reaction diagram
-
-
relative yield 0.8%
-
?
cyclohexylideneethyl diphosphate + isopentenyl diphosphate
10-cyclohexyliden-3,7-dimethyldeca-2,6-dien-1-ol + ?
show the reaction diagram
-
-
double condensation product, relative yield 23.1%
-
?
cyclohexylideneethyl diphosphate + isopentenyl diphosphate
10-cyclohexyliden-3,7-dimethyldeca-2,6-dien-1-ol + ?
show the reaction diagram
-
-
double condensation product, relative yield 3.0%
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
-
-
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
-
-
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
-
-
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
-
-
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
Q4JHN6
-
-
-
-
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
-
2 sequential irreversible 1', 4 condensations
-
-
ir
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
Pumpkin
-
activity is higher than with geranyl diphosphate
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
-
no activity with farnesyl diphosphate
-
-
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
Pumpkin
-
enzyme participates in isoprenoid biosynthesis in eukaryotes
-
-
-
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + diphosphate
show the reaction diagram
-
-
-
-
?
dimethylallyl diphosphate + 2 isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
the enzyme is bifunctional and produces (2E,6E)-farnesyl diphosphate or geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate depending on the divalent metal cofactor present. The enzyme is far more active with Co2+ as an additive than with any other tested metal ion. In the presence of Co2+ or Mn2+, with dimethylallyl diphosphate as a cosubstrate, it produces about 96% geranyl diphosphate and only 4% farnesyl diphosphate. In contrast, with Mg2+ as an additive, the enzyme produces 18% geranyl diphosphate and 82% farnesyl diphosphate
-
-
?
dimethylallyl diphosphate + geranyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
the enzyme is involved in the biosynthesis of the monoterpenoid precursors needed for formation of the defensive compound chrysomelidial. Farnesyl diphosphate serves as precursor for various primary metabolites and juvenile required hormone, the production of farnesyl diphosphate from dimethylallyl diphosphate and geranyl diphosphate is most active by addition of 0.5 mM Mg2+ compared with any other tested cofactor. At a constant 0.5 mM Co2+, and an ascending Mg2+ concentration, PcIDS1 displayed low farnesyl diphosphate forming activity. If Mg2+ is constant at 5 mM and Co2+ concentrations vary, high farnesyl diphosphate production can be observed only at Co2+ concentrations below 0.1 mM. As soon as the Co2+ concentration ascends, the farnesyl diphosphate-forming activity decreases dramatically. The Mg2+-catalyzed activity of the enzyme is abolished as soon as Co2+ reaches its optimal concentration
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + geranyl diphosphate
show the reaction diagram
-
-
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + geranyl diphosphate
show the reaction diagram
-
-
relative yield 100%
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + geranyl diphosphate
show the reaction diagram
-
key enzyme in isoprenoid biosynthesis, the synthase amino-acid residues at the 4th and 5th position before the first aspartate rich motif mainly determine product specificity
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + geranyl diphosphate
show the reaction diagram
-
when (R)-[2-2H]IPP is a substrate for chain elongation, no deuterium is found in the chain elongation products. In contrast, the deuterium in (S)-[2-2H]IPP is incorporated into all of the products. Thus, the pro-R hydrogen at C2 of IPP is lost when the E- and Z-double bond isomers are formed
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + trans,trans-farnesyl diphosphate
show the reaction diagram
-
-
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
(E,E)-farnesyl diphosphate + geranyl diphosphate + diphosphate
show the reaction diagram
-, Q1X876
-
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
(E,E)-farnesyl diphosphate + geranyl diphosphate + diphosphate
show the reaction diagram
Q1X877
-
ratio geranyl diphosphate/farnesyl diphosphate is about 2:1
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
(2E,6E)-farnesyl diphosphate + diphosphate
show the reaction diagram
-
-
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
G0YZR3, G0YZR4, -
-
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
B8XPY7, -
-
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
geranyl diphosphate + diphosphate
show the reaction diagram
Pumpkin
-
less than 5% of the activity with dimethylallyl diphosphate
-
-
?
geranyl diphosphate + 2-cyclohexenylethyl diphosphate
(S)-geranylcyclohexylideneethyl diphosphate + diphosphate
show the reaction diagram
-
-
relative yield 13.6%
-
?
geranyl diphosphate + 2-cyclohexenylethyl diphosphate
(S)-geranylcyclohexylideneethyl diphosphate + diphosphate
show the reaction diagram
-
-
relative yield 42.2%
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
-
-
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
-
ir
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
-
-
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
Pumpkin
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
E)-farnesyl diphosphate
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
-
-
E)-farnesyl diphosphate
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + trans,trans-farnesyl diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + trans,trans-farnesyl diphosphate
show the reaction diagram
-
no activity with dimethylallyl diphosphate
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + trans,trans-farnesyl diphosphate
show the reaction diagram
-
key enzyme in isoprenoid biosynthesis, the synthase amino-acid residues at the 4th and 5th position before the first aspartate rich motif mainly determine product specificity
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + trans,trans-farnesyl diphosphate
show the reaction diagram
-
small amounts of neryl diphosphate, (Z,E)-farnesyl diphosphate are formed along with the E-isomers. When (R)-[2-2H]IPP is a substrate for chain elongation, no deuterium is found in the chain elongation products. In contrast, the deuterium in (S)-[2-2H]IPP is incorporated into all of the products. Thus, the pro-R hydrogen at C2 of IPP is lost when the E- and Z-double bond isomers are formed
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (E,E)-farnesyl diphosphate
show the reaction diagram
Q4JHN6
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
Q197X6
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
Q08291
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
P08524, -
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
Q197X6
-
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
Geobacillus stearothermophilus ATCC 10149
Q08291
-
-
-
?
isopentenyl diphosphate + geranyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
Pumpkin
-
enzyme participates in isoprenoid biosynthesis in eukaryotes
-
-
-
isopentenyl diphosphate + geranyl diphosphate
(E,E)-farnesyl diphosphate + diphosphate
show the reaction diagram
-, Q1X876
-
-
-
?
methoxymethoxydimethylallyl diphosphate + isopentenyl diphosphate
methoxymethoxygeranyl diphosphate + diphosphate
show the reaction diagram
-
-
yield is 1% methoxymethoxygeranyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate
-
?
propoxygeranyl diphosphate + isopentenyl diphosphate
propoxyfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
yield is 3% methoxymethoxygeranyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate, and 63% yield for mutant Y81D, plus 6% of propoxygeranylgeranyl diphosphate
-
?
propoxygeranyl diphosphate + isopentenyl diphosphate
propoxyfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
yield is 62% methoxymethoxygeranyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate
-
?
vinyldimethylallyl diphosphate + isopentenyl diphosphate
vinylfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
sole product, yield is 29.9% vinylfarnesyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate
-
-
vinyldimethylallyl diphosphate + isopentenyl diphosphate
vinylgeranyl diphosphate + vinylfarnesyl diphosphate + diphosphate
show the reaction diagram
-
-
14.3% vinylgeranyl diphosphate plus 23.3% vinylfarnesyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate
-
-
methoxymethoxydimethylallyl diphosphate + isopentenyl diphosphate
methoxymethoxygeranyl diphosphate + diphosphate
show the reaction diagram
-
-
yield is 5% methoxymethoxygeranyl diphosphate, compared with 100% for the reaction of dimethylallyl diphosphate with isopentenyl diphosphate. Mutant Y81D yields methoxymethoxyfarnesyl diphosphate with high efficiency
-
?
additional information
?
-
-
no activity with dimethylallyl diphosphate
-
-
-
additional information
?
-
-, Q1X876
enzyme additionally shows geranyl diphosphate synthase and farnesyl diphosphate synthase activity
-
-
-
additional information
?
-
-, Q1X876
enzyme is able to produce farnesyl phosphate directly from geranyl phosphate, activity of farnesylgeranyltransferase
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
dimethylallyl diphosphate + 2 isopentenyl diphosphate
(E,E)-farnesyl diphosphate + 2 diphosphate
show the reaction diagram
Pumpkin
-
enzyme participates in isoprenoid biosynthesis in eukaryotes
-
-
-
dimethylallyl diphosphate + geranyl diphosphate
diphosphate + (2E,6E)-farnesyl diphosphate
show the reaction diagram
-
the enzyme is involved in the biosynthesis of the monoterpenoid precursors needed for formation of the defensive compound chrysomelidial. Farnesyl diphosphate serves as precursor for various primary metabolites and juvenile required hormone
-
-
?
dimethylallyl diphosphate + isopentenyl diphosphate
diphosphate + geranyl diphosphate
show the reaction diagram
-
key enzyme in isoprenoid biosynthesis
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + trans,trans-farnesyl diphosphate
show the reaction diagram
-
key enzyme in isoprenoid biosynthesis
-
-
?
isopentenyl diphosphate + geranyl diphosphate
diphosphate + farnesyl diphosphate
show the reaction diagram
Pumpkin
-
enzyme participates in isoprenoid biosynthesis in eukaryotes
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
18% of Mg2+ activation at 0.5 mM, inhibition above
Co2+
-
78% of Mg2+ activation at 1 mM
Co2+
-
with dimethylallyl diphosphate and isopentenyl diphosphate the enzyme is far more active with Co2+ as an additive than with any other tested metal ion. In the presence of Co2+ or Mn2+, with dimethylallyl diphosphate as a cosubstrate, the enzyme produces about 96% geranyl diphosphate and only 4% farnesyl diphosphate. In contrast, with Mg2+ as an additive, PcIDS1 produces 18% geranyl diphosphate and 82% farnesyl diphosphate
Fe2+
-
absolutely dependent on presence of divalent cation. Supports activity to a lower level than Mg2+
K+
-
stimulates with geranyl diphosphate as substrate
Mg2+
-
required for activity
Mg2+
Pumpkin
-
required for activity
Mg2+
-
maximum activity at 1-2 mM; required for activity
Mg2+
-
required for activity
Mg2+
-
maximal activity at 1 mM; required for activity
Mg2+
-
absolutely dependent on presence of divalent cation. Optimal activity at 4-10 mM
Mg2+
-
; presence of one Mg2+ in complex of enzyme with inhibitor [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid)
Mg2+
-
required
Mg2+
-
with the substrates dimethylallyl diphosphate and isopentenyl diphosphate the enzyme is far more active with Co2+ as an additive than with any other tested metal ion. In the presence of Co2+ or Mn2+, with dimethylallyl diphosphate as a cosubstrate, the enzyme produces about 96% geranyl diphosphate and only 4% farnesyl diphosphate. In contrast, with Mg2+ as an additive, PcIDS1 produces 18% geranyl diphosphate and 82% farnesyl diphosphate. The production of farnesyl diphosphate from dimethylallyl diphosphate and geranyl diphosphate is most active by addition of 0.5 mM Mg2+ compared with any other tested cofactor. At a constant 0.5 mM Co2+, and an ascending Mg2+ concentration, PcIDS1 displayed low farnesyl diphosphate forming activity. If Mg2+ is constant at 5 mM and Co2+ concentrations vary, high farnesyl diphosphate production can be observed only at Co2+ concentrations below 0.1 mM. As soon as the Co2+ concentration ascends, the farnesyl diphosphate-forming activity decreases dramatically. The Mg2+-catalyzed activity of the enzyme is abolished as soon as Co2+ reaches its optimal concentration
Mg2+
P08524
contains 3 Mg2+ ions
Mn2+
-
can partially replace Mg2+, less effective
Mn2+
Pumpkin
-
can partially replace Mg2+, less effective
Mn2+
-
activation at 0.25-0.50 mM, inhibition above
Mn2+
-
-
Mn2+
-
can replace Mg2+, maximal activity at 0.1 mM, inhibition above
Ni2+
-
10% of Mg2+ activation at 0.5 mM, inhibition above
Zn2+
-
91% of Mg2+ activation at 0.5 mM, almost complete inhibition at 5 mM
Mn2+
-
absolutely dependent on presence of divalent cation. Supports activity to a lower level than Mg2+
additional information
-
not activated by Na+ or Li+
additional information
-
the enzyme is inactive without adding divalent metal cations
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(1-hydroxyheptane-1,1-diyl)bis(phosphonic acid)
-
-
(2-[[(2E)-2,6-dimethylhepta-2,5-dien-1-yl]amino]ethane-1,1-diyl)bis(phosphonic acid)
-
-
([Cu(II)(pamidronate)]H2O)n
-
-
-
([[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]amino]methanediyl)bis(phosphonic acid)
-
-
([[6-(3-methoxyphenyl)pyridin-3-yl]amino]methanediyl)bis(phosphonic acid)
-
-
([[6-(thiophen-3-yl)pyridin-3-yl]amino]methanediyl)bis(phosphonic acid)
-
-
1-[(benzylamino)ethyl] 1,1-bisphosphonic acid
-
-
-
1-[(n-dec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
-
1-[(n-dodec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
-
1-[(n-hept-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
1-[(n-hex-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
1-[(n-non-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
-
1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
1-[(n-pent-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
1-[(n-tetradec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
-
1-[(n-undec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
-
1-[(prop-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
1-[(prop-2-ylamino)ethyl] 1,1-bisphosphonic acid
-
-
3-(2-hydroxy-2,2-diphosphonoethyl)-2H-imidazo[1,2-a]pyridin-4-ium
-
-
alendronate
-
twelve weeks of alendronate treatment 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
alendronate
-
i.e. 4-amino-1-hydroxybutane-1,1-diylphosphonic acid
Ca2+
-
5 mM, 80% inhibition
diphosphate
-
0.66 mM, 50% inhibition
farnesyl diphosphate
-
0.06 mM, 50% inhibition
geranyl diphosphate
-
-
iodoacetamide
Pumpkin
-
5 mM, 31% inhibition
iodoacetamide
-
8 mM, 33% inhibition
isopentenyl diphosphate
-
-
isopentenyl diphosphate
-
substrate inhibition
K+
-
500 mM, 63% inhibition in the presence of MgCl2
Mn2+
-
activates at 0.25-0.50 mM, inhibition above
N-ethylmaleimide
-
8 mM, 54% inhibition
p-chloromercuribenzoic acid
-
0.15 mM, 882% inhibition of wild-type farnesyl diphosphate synthase, 11% inhibition of C73S/C289S mutant enzyme
p-hydroxymercuribenzoate
-
1 mM, 25% inhibition
palmidronate
-
-
-
pamidronate
-
i.e. 3-amino-1-hydroxypropane-1,1-diylphosphonic acid
Phenylglyoxal
-
-
residronate
-
-
-
risedronate
-
about 98% inhibition at 100 mM
risedronate
-
i.e. 1-hydroxy-2-(pyridin-3-yl)ethane-1,1-diylphosphonic acid
[(octylamino)methanediyl]bis(phosphonic acid)
-
-
[([6-[3-(trifluoromethyl)phenyl]pyridin-3-yl]amino)methanediyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[2-(1H-indazol-4-yl)pyridin-4-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-indazol-4-yl)pyridin-2-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-indazol-4-yl)pyridin-3-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-indazol-5-yl)pyridin-2-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-indazol-5-yl)pyridin-3-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-indazol-6-yl)pyridin-3-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-pyrazol-4-yl)pyridin-2-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[5-(1H-pyrazol-4-yl)pyridin-3-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-fluoro-2-[6-(1H-pyrazol-4-yl)pyridin-3-yl]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-hydroxy-3-[(3-phenylpropyl)amino]propane-1,1-diyl]bis(phosphonic acid)
-
-
[1-hydroxy-3-[methyl(2-phenylethyl)amino]propane-1,1-diyl]bis(phosphonic acid)
-
-
[1-hydroxy-3-[methyl(4-phenylbutyl)amino]propane-1,1-diyl]bis(phosphonic acid)
-
-
[2-(3-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
-
[2-(3-fluorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
-
[2-(cyclohexylamino)ethane-1,1-diyl]bisphosphonic acid
-
-
-
[2-(heptylamino)ethane-1,1-diyl]bis(phosphonic acid)
-
-
[2-(hexylamino)ethane-1,1-diyl]bis(phosphonic acid)
-
competitive inhibitor
[2-(n-heptylamino)ethane-1,1-diyl]bisphosphonic acid
-
-
-
[2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid
-
-
-
[2-(n-pentylamino)ethane-1,1-diyl]bisphosphonic acid
-
-
-
[2-(npropylamino)ethane-1,1-diyl]bisphosphonic acid
-
-
-
[2-[(2-methylprop-2-en-1-yl)amino]ethane-1,1-diyl]bis(phosphonic acid)
-
-
[2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)pyridin-4-yl]-1-fluoroethane-1,1-diyl]bis(phosphonic acid)
-
-
[2-[5-(3,5-dimethyl-1,2-oxazol-4-yl)pyridin-3-yl]-1-fluoroethane-1,1-diyl]bis(phosphonic acid)
-
-
[2-[6-(3,5-dimethyl-1,2-oxazol-4-yl)pyridin-2-yl]-1-fluoroethane-1,1-diyl]bis(phosphonic acid)
-
-
[6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid)
-
i.e. NE-10501, chiral analog of risedronate. Crystallization of human enzyme from a solution of racemic NE-10501 results in a complex containing the R enantiomer in the enzyme active site
[Co(II)(pamidronate)2(H2O)2]
-
-
-
[Co(II)(risedronate)2]
-
-
-
[Co(II)2(alendronate)4(H2O)2]
-
-
-
[Cu(II)(risedronate)2]
-
-
-
[Cu(II)2(alendronate)4(H2O)2]
-
-
-
[Mn(II)(pamidronate)2(H2O)2]
-
-
-
[Mn(II)(risedronate)2]
-
-
-
[Mn(II)2(alendronate)4(H2O)2]
-
-
-
[Ni(II)(pamidronate)2(H2O)2]
-
-
-
[Ni(II)(risedronate)2]
-
-
-
[Ni(II)2(alendronate)4(H2O)2]
-
-
-
Mn2+
-
strong inhibition above 0.1 mM, activation below
additional information
-
neither iodoacetamide nor N-ethylmaleimide inhibits at concentration less than 5 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,4-dithiothreitol
-
2 mM, 1.6fold stimulation
2-mercaptoethanol
-
10 mM, 1.2fold stimulation
dithioerythritol
-
-
NH4+
-
3fold stimulation with geranyl diphosphate as substrate; 5fold stimulation with dimethylallyl diphosphate as substrate
Triton X-100
-
0.5%, 3fold activation
Triton X-100
-
0.2%, 1.5fold increase in activity
Tween 80
-
0.5%, 2.3fold activation
dithiothreitol
-
2.5 mM, increases activity 2fold
additional information
-
not activated by Tween 20, Triton X-100, Chaps or Nonidet P-40
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0045
-
dimethylallyl diphosphate
-
0.042-0.056 mg/ml protein, isoenzyme II, Km values depend on protein concentration
0.0059
-
dimethylallyl diphosphate
-
0.042-0.056 mg/ml protein, isoenzyme I, Km values depend on protein concentration
0.009
-
dimethylallyl diphosphate
-
-
0.0159
-
dimethylallyl diphosphate
-
mutant enzyme L58A
0.05
-
dimethylallyl diphosphate
-
-
0.0666
-
dimethylallyl diphosphate
-
wild-type enzyme
0.0705
-
farnesyl diphosphate
-
mutant enzyme L58A
0.0012
-
geranyl diphosphate
-
fixed substrate isopentenyl diphosphate (0.05 mM), pH and temperature not specified in the publication, metal cofactor: Mg2+
0.0013
-
geranyl diphosphate
Pumpkin
-
-
0.0018
-
geranyl diphosphate
-
-
0.0098
-
geranyl diphosphate
-
pH 7.9, 37C
0.018
-
geranyl diphosphate
-
-
0.0243
-
geranyl diphosphate
-
fixed substrate isopentenyl diphosphate (0.05 mM), pH and temperature not specified in the publication, metal cofactor: Co2+
0.036
-
geranyl diphosphate
-
0.042-0.056 mg/ml protein, isoenzyme I, Km values depend on protein concentration
0.039
-
geranyl diphosphate
-
0.042-0.056 mg/ml protein, isoenzyme II, Km values depend on protein concentration
4.9
-
geranyl diphosphate
-
C73F mutant enzyme at 45C
5.6
-
geranyl diphosphate
-
C73S/C289S mutant enzyme at 55C
5.8
-
geranyl diphosphate
-
wild-type enzyme at 45C
6.4
-
geranyl diphosphate
-
C289S mutant enzyme at 55C
7.3
-
geranyl diphosphate
-
C73F mutant enzyme at 55C
7.5
-
geranyl diphosphate
-
C289F mutant enzyme at 55C
8.4
-
geranyl diphosphate
-
wild-type enzyme at 55C
0.0015
-
isopentenyl diphosphate
-
fixed substrate geranyl diphosphate (0.05 mM), pH and temperature not specified in the publication, metal cofactor: Co2+
0.007
-
isopentenyl diphosphate
-
fixed substrate geranyl diphosphate (0.05 mM), pH and temperature not specified in the publication, metal cofactor: Mg2+
0.0153
-
isopentenyl diphosphate
-
-
0.032
-
isopentenyl diphosphate
-
0.042-0.056 mg/ml protein, isoenzyme II, Km values depend on protein concentration
0.043
-
isopentenyl diphosphate
-
pH 7.9, 37C
0.048
-
isopentenyl diphosphate
-
0.042-0.056 mg/ml protein, isoenzyme I, Km values depend on protein concentration
0.0531
-
isopentenyl diphosphate
-
cosubstrate: dimethylallyl diphosphate, wild-type enzyme
0.221
-
isopentenyl diphosphate
-
cosubstrate: farnesyl diphosphate, mutant enzyme L58A
4.7
-
isopentenyl diphosphate
-
wild-type enzyme at 45C
4.8
-
isopentenyl diphosphate
-
C73F mutant enzyme at 45C
11.6
-
isopentenyl diphosphate
-
C73F mutant enzyme at 55C
13
-
isopentenyl diphosphate
-
wild-type enzyme at 55C
13.3
-
isopentenyl diphosphate
-
C73S/C289S mutant enzyme at 55C
14.3
-
isopentenyl diphosphate
-
C289S mutant enzyme at 55C
130
-
isopentenyl diphosphate
-
C289F mutant enzyme at 55C
0.0712
-
Mg2+
-
-
0.0445
-
Mn2+
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.2
-
geranyl diphosphate
-
pH 7.9, 37C
0.49
-
isopentenyl diphosphate
-
pH 7.9, 37C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.322
-
geranyl diphosphate
-
fixed substrate isopentenyl diphosphate (0.05 mM), pH and temperature not specified in the publication, metal cofactor: Mg2+
0.0007
-
isopentenyl diphosphate
-
-
1.05
-
isopentenyl diphosphate
-
fixed substrate geranyl diphosphate (0.05 mM), pH and temperature not specified in the publication, metal cofactor: Mg2+
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00063
-
(1-hydroxyheptane-1,1-diyl)bis(phosphonic acid)
-
pH 7.4, 22C
0.000095
-
([Cu(II)(pamidronate)]H2O)n
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.001
-
1-[(benzylamino)ethyl] 1,1-bisphosphonic acid
-
IC50 above 0.001 mM, in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000068
-
1-[(n-dec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.001
-
1-[(n-dec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
IC50 above 0.001 mM, in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000093
-
1-[(n-dodec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000811
-
1-[(n-dodec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000058
-
1-[(n-hept-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.000095
-
1-[(n-hept-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.000137
-
1-[(n-hex-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.00049
-
1-[(n-hex-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.00043
-
1-[(n-non-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.00044
-
1-[(n-non-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000087
-
1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.00101
-
1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.00008
-
1-[(n-pent-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.000292
-
1-[(n-tetradec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
IC50 above 0.001 mM, in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.001
-
1-[(n-tetradec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
IC50 above 0.001 mM, in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000856
-
1-[(n-undec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000868
-
1-[(n-undec-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000038
-
1-[(prop-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.000298
-
1-[(prop-1-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.000013
-
1-[(prop-2-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.000337
-
1-[(prop-2-ylamino)ethyl] 1,1-bisphosphonic acid
-
pH 7.4, 37C
0.00064
-
3-(2-hydroxy-2,2-diphosphonoethyl)-2H-imidazo[1,2-a]pyridin-4-ium
-
pH 7.4, 22C
0.0044
-
alendronate
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
0.00134
-
pamidronate
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
0.000027
-
risedronate
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
0.000074
-
risedronate
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
0.00049
-
[(octylamino)methanediyl]bis(phosphonic acid)
-
pH 7.4, 22C
0.00045
-
[1-hydroxy-3-[(3-phenylpropyl)amino]propane-1,1-diyl]bis(phosphonic acid)
-
pH 7.4, 22C
0.0004
-
[1-hydroxy-3-[methyl(2-phenylethyl)amino]propane-1,1-diyl]bis(phosphonic acid)
-
pH 7.4, 22C
0.00061
-
[1-hydroxy-3-[methyl(4-phenylbutyl)amino]propane-1,1-diyl]bis(phosphonic acid)
-
pH 7.4, 22C
0.00063
-
[2-(3-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
pH 7.4, 22C
0.00063
-
[2-(3-fluorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
pH 7.4, 22C
0.000058
-
[2-(heptylamino)ethane-1,1-diyl]bis(phosphonic acid)
-
pH and temperature not specified in the publication
0.00014
-
[2-(hexylamino)ethane-1,1-diyl]bis(phosphonic acid)
-
pH and temperature not specified in the publication
0.00135
-
[2-(hexylamino)ethane-1,1-diyl]bis(phosphonic acid)
-
pH and temperature not specified in the publication
0.000058
-
[2-(n-heptylamino)ethane-1,1-diyl]bisphosphonic acid
-
pH and temperature not specified in the publication
-
0.00049
-
[2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid
-
pH and temperature not specified in the publication
-
0.00184
-
[2-(n-pentylamino)ethane-1,1-diyl]bisphosphonic acid
-
pH and temperature not specified in the publication
-
0.000038
-
[2-(npropylamino)ethane-1,1-diyl]bisphosphonic acid
-
pH and temperature not specified in the publication
-
0.0006295
-
[6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid)
-
racemat
0.000215
-
[Co(II)(pamidronate)2(H2O)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.0001
-
[Co(II)(risedronate)2]
-
IC50 above 0.0001 mM, in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.05
-
[Co(II)2(alendronate)4(H2O)2]
-
IC50 above 0.05 mM, in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000026
-
[Cu(II)(risedronate)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000717
-
[Cu(II)2(alendronate)4(H2O)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000161
-
[Mn(II)(pamidronate)2(H2O)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.0000027
-
[Mn(II)(risedronate)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000128
-
[Mn(II)2(alendronate)4(H2O)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000328
-
[Ni(II)(pamidronate)2(H2O)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.0000029
-
[Ni(II)(risedronate)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
0.000167
-
[Ni(II)2(alendronate)4(H2O)2]
-
in 10 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM dithiothreitol, at 37C
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0012
-
-
-
0.04
-
-
isoenzyme II
0.06
-
-
isoenzyme I
0.35
-
-
C289F mutant enzyme at 55C
0.922
-
-
-
1.3
-
-
C73F mutant enzyme at 45C
1.85
-
-
-
2.61
-
-
wild-type enzyme at 45C
3.94
-
-
C289S mutant enzyme at 55C
3.97
-
-
C73S/C289S mutant enzyme at 55C
4.3
-
-
C73F mutant enzyme at 55C
4.69
-
-
wild-type enzyme at 55C
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.3
8.8
-
-
7.5
8
-
-
7.5
-
Pumpkin
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
8.5
-
approx. 45% of maximal activity at pH 5.5, approx. 60% of activity maximum at pH 8.5, emzyme I
7
10
-
active over the range pH 7-10
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.6
-
G0YZR3, G0YZR4, -
isoform FPPS2, calculated from amino acid sequence
7.5
-
G0YZR3, G0YZR4, -
isoform FPPS1, calculated from amino acid sequence
8.63
-
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Pumpkin
-
-
Manually annotated by BRENDA team
Q4JHN6
and seed, high expression
Manually annotated by BRENDA team
Q4JHN6
and stem, low expression
Manually annotated by BRENDA team
Q4JHN6
hairy root and seed, high expression
Manually annotated by BRENDA team
Q4JHN6
and hairy root, high expression; and root, high expression
Manually annotated by BRENDA team
Q4JHN6
and leaf, low expression
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Agrobacterium tumefaciens (strain C58 / ATCC 33970)
Campylobacter jejuni (strain RM1221)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Lactobacillus brevis (strain ATCC 367 / JCM 1170)
Lactobacillus brevis (strain ATCC 367 / JCM 1170)
Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
Methylococcus capsulatus (strain ATCC 33009 / NCIMB 11132 / Bath)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas fluorescens (strain Pf-5 / ATCC BAA-477)
Pseudomonas fluorescens (strain Pf-5 / ATCC BAA-477)
Pseudomonas fluorescens (strain Pf-5 / ATCC BAA-477)
Roseobacter denitrificans (strain ATCC 33942 / OCh 114)
Roseobacter denitrificans (strain ATCC 33942 / OCh 114)
Streptococcus uberis (strain ATCC BAA-854 / 0140J)
Streptococcus uberis (strain ATCC BAA-854 / 0140J)
Zymomonas mobilis subsp. mobilis (strain ATCC 31821 / ZM4 / CP4)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
56000
-
-
gel filtration, enzyme I, protein concentration 0.02 mg/ml
60000
-
-
gel filtration, enzyme II, protein concentration 0.02 mg/ml
67000
-
-
gel filtration
72500
-
-
gel filtration, protein concentration 25 mg/ml
74000
-
-
gel filtration
87600
-
-
enzyme-Co2+ complex, gel filtration
93800
-
-
enzyme-Mg2+ complex, gel filtration
103000
-
-
SDS-PAGE after cross-linking with dimethyl suberimidate
110000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Q4JHN6
x * 56000, recombinant protein with tags
?
-
x * 58000, native enzyme, SDS-PAGE; x * 69600, calculated from amino acid sequence; x * 75000, recombinant enzyme, SDS-PAGE
?
Q42698
x * 39900, calculated from amino acid sequence
?
B8XPY7, -
x * 100000, SDS-PAGE
?
-
x * 58000, native enzyme, SDS-PAGE; x * 69600, calculated from amino acid sequence; x * 75000, recombinant enzyme, SDS-PAGE
-
dimer
-
2 * 50000, calculated, 2 * 47000, SDS-PAGE
dimer
Q8WS25
crystallization data
dimer
-
2 * 45800, the enzyme is always present as a dimer regardless of the added cofactor, in the case of Mg2+, the dimeric protein possesses the largest volume (93800 Da), most likely due to a more relaxed conformation. With Co2+, the enzyme seems to have a more compact conformation (87600 Da), which may be responsible for the change in product spectrum calculated from sequence
homodimer
G0YZR3, G0YZR4, -
2 * 45500, isoform FPPS1, calculated from amino acid sequence; 2 * 45900, isoform FPPS2, calculated from amino acid sequence
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
molecular dynamics simulations for wild-type and mutants Q107E, L110W, Q107F, Q107F/L110A, L110A
Q1X877
molecular modeling of structure based on PDB file 1FPS
-
crystallization of human enzyme from a solution of racemic [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) results in a complex containing the R enantiomer in the enzyme active site. Contrary to known complexes of enzyme with risedronate, zoledronate, and minodronate, the complex with [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) displays only one Mg2+ ion; in complex with chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid), i.e. NE-10501. The complex contains the R enantiomer in the enzymic active site, which is confirmed by docking studies. Presence of one Mg2+
-
in complex with Mg2+ and inhibitors, vapor diffusion method, using 100 mM sodium acetate, pH 4.6-5.2, 200 mM ammonium sulfate, and 2-10% (w/v) PEG 4K
-
in complex with substrate isopentenyl diphosphate and five nitrogen-containing bisphosphonate inhibitors. The C1-hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of isopentenyl diphosphate and the conformation of residues Y94 and Q167. binding of the inhibitors changes the binding properties of the second site of the dimer
Q8WS25
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
55
-
-
wild-type: stable for 30 min, C73F mutant: complete loss of activity after 20 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
thiol reducing agents are detrimental for stability
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme seems to be susceptible to oxidation when treated with Cu2+, forming an intrasubunit disulfide bond rather than intersubunit bonds
-
638699
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, 3 months, no loss of activity
-
-20C, at least 1 week, no loss of activity
-
4C, 5 days, 36% loss of activity
-
4C, precipitate in neutral (NH4)2SO4 solution at 60% saturation, 1 year, 50-70% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DEAE-Sepharose, Mono Q, phenyl-Sepharose
-
ammonium sulfate, Sephadex G-100, hydroxylapatite, DEAE-Sephadex A-50
-
Ni-NTA column chromatography
B8XPY7, -
ammonium sulfate, affinity chromatography
-
partial purification
-
recombinant protein
Q4JHN6
ammonium sulfate, Sephadex G 200, hydroxylapatite
Pumpkin
-
TALON resin Co2+ metal affinity column chromatography; TALON resin Co2+ metal affinity column chromatography
G0YZR3, G0YZR4, -
ammonium sulfate, affinity chromatography
-
anti-FLAG M2 affinity resin chromatography and nickel affinity column chromatography
-
HisTrap Ni2+ chelate affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expressed in Saccharomyces cerevisiae
Q42698
expressed in Escherichia coli ArcticExpress (DE3) RP cells
B8XPY7, -
expressed in Escherichia coli DH5alpha cells
Q08291
expression of wild-type, S82F, S82Y, S82W, L83F, L83Y, I84F and I84Y mutant enzymes in Escherichia coli
-
overexpression of C73F, C289F, C73S, C289S and C73/C289S mutant enzyme in Escherichia coli
-
expressed in Escherichia coli
-
expression in Mycobacterium smegmatis using a new mycobacterial expression vector that encodes an in-frame N-terminal affinity tag fusion with the protein of interest
-
expression in Escherichia coli
Q4JHN6
expression in Escherichia coli after truncation of the signal sequence at the 5'-end of the coding region
-
expression in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells; expressed in Escherichia coli BL21(DE3) cells
G0YZR3, G0YZR4, -
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21(DE3) cells
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme expression in stage 2 of flower development is 22fold higher than in the stage 2, and these levels rise dramatically in the flower of stage 3 and 4, reaching a 113fold increase at stage 4
B8XPY7, -
after treatment of hairy root with methyl jasmonate, mRNA is detected within 12 h and achieves a maximum after 24 h
Q4JHN6
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
L110A
Q1X877
complete loss of activity
L110W
Q1X877
about 50% decrease in reaction rate, increase in production of geranyl diphosphate
Q107E
Q1X877
increase in production of geranyl diphosphate
Q107F
Q1X877
increase in production of farnesyl diphosphate
C289F
-
approx. 1/13 of wild-type activity at 55C
C289S
-
similar activity like wild-type
C73F
-
heat sensitive mutant
C73S
-
similar activity like wild-type
C73S/C289S
-
similar activity like wild-type
F220A
-
100000fold decrease in catalytic activity
I84F
-
7.2% of wild-type activity with dimethylallyl diphosphate
I84Y
-
similiar activity as wild-type
L83F
-
similiar activity as wild-type
L83Y
-
similiar activity as wild-type
Q221E
-
1000fold decrease in catalytic activity
R295V
-
no marked change in catalytic activity
S82F
-
produces exclusively geranyl diphosphate, i.e. the mutant enzyme has changed from a farnesyl diphosphate synthase to a geranyl diphosphate synthase
S82W
-
no prenyl transferase activity
S82Y
-
similiar activity as wild-type
Y81D
-
contrary to wild-type, reaction of (Z)-ethynyldimethylallyl diphosphate plus isopentenyl diphosphate yields a mixture of products ethynylgeranyl, ethynylfarnesyl, and ethynylgeranylgeranyl diphosphates
Y81D
-
mutant yields higher condensation products than wild-type
Y81S
Q08291
the mutant catalyzes the reaction between 8-tetrahydropyran-2-yloxygeranyl diphosphate and isopentenyl diphosphate, producing 12-tetrahydropyran-2-yloxyfarnesyl diphosphate with a yield of 12.3%. The mutant catalyzes the reaction between 8-acetoxygeranyl diphosphate with isopentenyl diphosphate, producing 12-acetoxyfarnesyl diphosphate and 16-acetoxygeranylgeranyl diphosphate with respective yields of 55.3% and 1.7%
Y81S
Geobacillus stearothermophilus ATCC 10149
-
the mutant catalyzes the reaction between 8-tetrahydropyran-2-yloxygeranyl diphosphate and isopentenyl diphosphate, producing 12-tetrahydropyran-2-yloxyfarnesyl diphosphate with a yield of 12.3%. The mutant catalyzes the reaction between 8-acetoxygeranyl diphosphate with isopentenyl diphosphate, producing 12-acetoxyfarnesyl diphosphate and 16-acetoxygeranylgeranyl diphosphate with respective yields of 55.3% and 1.7%
-
K266I
G0YZR3, G0YZR4, -
the mutation abolishes the activities of isoform FPPS1; the mutation abolishes the activities of isoform FPPS2
R120G
G0YZR3, G0YZR4, -
the mutation abolishes the activities of isoform FPPS1; the mutation abolishes the activities of isoform FPPS2
R121G
G0YZR3, G0YZR4, -
the mutation abolishes the activities of isoform FPPS1; the mutation abolishes the activities of isoform FPPS2
K254A/K197G
P08524
the mutations result in a loss of enzyme activity and a lethal phenotype
K254E/K197G
P08524
the mutations result in a loss of enzyme activity and a lethal phenotype
S50L
-
mutant enzyme produces prenyl diphosphates with the same chain lengths as the wild-type enzyme does. 1.3-1.4fold decrease in ratio of Vmax to Km-value for dimethylallyl diphosphate and isopentenyl diphosphate
Y81D
-
contrary to wild-type, reaction of (Z)-ethynyldimethylallyl diphosphate plus isopentenyl diphosphate yields a mixture of products ethynylgeranyl, ethynylfarnesyl, and ethynylgeranylgeranyl diphosphates
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
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
medicine
-
chronic treatment with an FPPS inhibitor attenuates the development of cardiac hypertrophy and fibrosis
medicine
-
the enzyme is a target for Chagas disease chemotherapy