Information on EC 2.5.1.68 - (2Z,6E)-farnesyl diphosphate synthase

Word Map on EC 2.5.1.68
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
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 enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.5.1.68
-
RECOMMENDED NAME
GeneOntology No.
(2Z,6E)-farnesyl diphosphate synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2Z,6E)-farnesyl diphosphate
show the reaction diagram
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
mono-trans, poly-cis decaprenyl phosphate biosynthesis
-
-
Terpenoid backbone biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
geranyl-diphosphate:isopentenyl-diphosphate geranylcistransferase
Requires Mg2+ or Mn2+ for activity. The product of this reaction is an intermediate in the synthesis of decaprenyl phosphate, which plays a central role in the biosynthesis of most features of the mycobacterial cell wall, including peptidoglycan, linker unit galactan and arabinan. Neryl diphosphate can also act as substrate.
CAS REGISTRY NUMBER
COMMENTARY hide
300811-47-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(E)-geranyl diphosphate + isopentenyl diphosphate
(2Z,6E)-farnesyl diphosphate + diphosphate
show the reaction diagram
(E)-neryl diphosphate + isopentenyl diphosphate
(2Z,6Z)-farnesyl diphosphate + diphosphate
show the reaction diagram
(E,E)-farnesyl diphosphate + isopentenyl diphosphate
? + diphosphate
show the reaction diagram
8-hydroxygeranyl diphosphate + isopentenyl diphosphate
(2Z)-12-hydroxyfarnesyl diphosphate + (2Z, 6Z)-16-hydroxygeranylgeranyl diphosphate + diphosphate
show the reaction diagram
-
16.7% yield of (2Z)-12-hydroxyfarnesyl diphosphate, 6.6% yield of (2Z, 6Z)-16-hydroxygeranylgeranyl diphosphate
-
?
geranyl diphosphate + isopentenyl diphosphate
(2Z,6E)-farnesyl diphosphate + diphosphate
show the reaction diagram
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2Z,6E)-farnesyl diphosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(E)-geranyl diphosphate + isopentenyl diphosphate
(2Z,6E)-farnesyl diphosphate + diphosphate
show the reaction diagram
geranyl diphosphate + isopentenyl diphosphate
(2Z,6E)-farnesyl diphosphate + diphosphate
show the reaction diagram
geranyl diphosphate + isopentenyl diphosphate
diphosphate + (2Z,6E)-farnesyl diphosphate
show the reaction diagram
-
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
-
optimal at 0.1 mM, the enzyme absolutely requires a divalent cation, inhibition by Mn2+ at higher concentration of 1.0-5.0 mM
additional information
-
no activation by Zn2+ and Ca2+ up to 5 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1-[[(3E)-4,8-dimethylnona-3,7-dien-1-yl](hydroxy)phosphoryl]-1-ethylpropyl)phosphonic acid
-
-
(E)-1-ethyl-1-[(4,8-dimethyl-3,7-nonadienyl)hydroxyphosphoryl] propyl phosphonic acid tripotassium salt
-
-
(E)-geranyl diphosphate analogues
-
design and synthesis of substrate analogue inhibitors, overview
-
citronellyl diphosphate
-
-
EDTA
-
complete inhibition at 10 mM
Mn2+
-
optimal at 0.1 mM, the enzyme absolutely requires a divalent cation, inhibition by Mn2+ at higher concentration of 5.0 mM
additional information
-
no inhibition by dipotassium salt of (E)-1-[(3,7-methyl-2,6-octadienyl)aminocarbonyl] propyl phosphonic acid, dipotassium salt of (E)-1-[[(3,7-methyl-2,6-octadienyl)oxy]aminocarbonyl] propyl phosphonic acid, and dipotassium salt of (E)-2-oxo-2-[(3,7-methyl-2,6-octadienyl)oxy-[amino]ethyl]phosphonic acid
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.038
(E)-geranyl diphosphate
-
pH 7.9, 37C
0.016
(E)-neryl diphosphate
-
pH 7.9, 37C
0.0023 - 0.15
geranyl diphosphate
0.0012 - 0.124
isopentenyl diphosphate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
141 - 860
geranyl diphosphate
173 - 788
isopentenyl diphosphate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
34390 - 110300
geranyl diphosphate
175
49100 - 235000
isopentenyl diphosphate
113
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0007
-
in presence of 1.0 mM Mg2+
0.00093
-
recombinant Rv1086 in cytosol of Mycobacterium smegmatis
0.00097
-
recombinant Rv1086 in membranes of Mycobacterium smegmatis
0.0014
-
in presence of 0.1 mM Mn2+
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallization using sparse matrix screens and vapor diffusion, structure of apo Rv1086 with citronellyl diphosphate bound and with the product mimic (2E,6E)-farnesyl diphosphate bound. The maximal reaction rate of the wild-type enzyme is 10fold greater than that of the mutant enzyme; in complex with citronellyl diphosphate and with product mimic (E,E)-farnesyl diphosphate
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His Trap column chromatography
native enzyme in a single step by chitin affinity chromatography
-
nickel-chelating affinity column chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli SN-IRv cells
-
expression in Escherichia coli
Rv1086, DNA and amino acid sequence determination and anaylsis, overexpression in Mycobacterium smegmatis cytosol and membranes, the transformed cells show a 5fold increased enzyme activity
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
L84A
-
potentially important in limiting chain length. The mutant L84A is not expressed in a soluble form
L84A/L85F
-
mutant enzyme has a Km-value for geranyl diphosphate of 0.15 mM compared to 0.038 mM for wild-type Rv108612; well expressed and active. Mutant protein is capable of synthesizing prenyl diphosphates containing 20 carbon atoms when geranyl diphosphate is used as the allylic substrate and 50 carbon atoms when EE-farnesyl diphosphate is used as the allylic substrate
L84A
-
potentially important in limiting chain length. The mutant L84A is not expressed in a soluble form
-
L84A/L85F
-
mutant enzyme has a Km-value for geranyl diphosphate of 0.15 mM compared to 0.038 mM for wild-type Rv108612; well expressed and active. Mutant protein is capable of synthesizing prenyl diphosphates containing 20 carbon atoms when geranyl diphosphate is used as the allylic substrate and 50 carbon atoms when EE-farnesyl diphosphate is used as the allylic substrate
-
I59A
-
change in product chain-length, produces prenyl products with chain length up to C50
I59F
-
inactive mutant enzyme
I59M
-
change in product chain-length, produces prenyl products with chain length up to C50
I59V
-
change in product chain-length, produces prenyl products with chain length up to C50