Information on EC 2.5.1.83 - hexaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific]

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The expected taxonomic range for this enzyme is: Micrococcus luteus

EC NUMBER
COMMENTARY hide
2.5.1.83
-
RECOMMENDED NAME
GeneOntology No.
hexaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific]
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(2E,6E)-farnesyl diphosphate + 3 isopentenyl diphosphate = 3 diphosphate + all-trans-hexaprenyl diphosphate
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
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hexaprenyl diphosphate biosynthesis
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Terpenoid backbone biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
(2E,6E)-farnesyl-diphosphate:isopentenyl-diphosphate farnesyltranstransferase (adding 3 isopentenyl units)
The enzyme prefers farnesyl diphosphate to geranylgeranyl diphosphate as an allylic substrate and does not show activity for geranyl diphosphate and dimethylallyl diphosphate [1].
CAS REGISTRY NUMBER
COMMENTARY hide
83745-07-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
O66127: component A of hexaprenyl diphosphate synthase, O66129: component B of hexaprenyl diphosphate synthase; strain B-P 26
O66127 and O66129
UniProt
Manually annotated by BRENDA team
O66127: component A of hexaprenyl diphosphate synthase, O66129: component B of hexaprenyl diphosphate synthase; strain BP-26
O66127 and O66129
UniProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + 1 but-3-enyl diphosphate
diphosphate + (E)-norgeranylgeranyl diphosphate
show the reaction diagram
(2E,6E)-farnesyl diphosphate + 3 isopentenyl diphosphate
3 diphosphate + all-trans-hexaprenyl diphosphate
show the reaction diagram
(2E,6E)-farnesyl diphosphate + 3-ethylbut-3-enyl diphosphate
diphosphate + (all-E)-3-ethyl-7,11,15-trimethylhexadeca-2,6,10,14-tetraenyl diphosphate + (all-E)-3,7-diethyl-11,15,19-trimethyleicosa-2,6,10,14,18-pentaenyl diphosphate
show the reaction diagram
(2E,6E)-farnesyl diphosphate + 3-ethylbut-3-enyl diphosphate
diphosphate + (all-E)-3-ethyl-7,11,15-trimethylhexadeca-2,6,10,14-tetraenyl diphosphate + (all-E)-3,7-diethyl-11,15,19-trimethylicosa-2,6,10,14,18-pentaenyl diphosphate
show the reaction diagram
(2E,6E)-farnesyl diphosphate + 3-propylbut-3-enyl diphosphate
?
show the reaction diagram
(2E,6E)-farnesyl diphosphate + but-3-enyl diphosphate
diphosphate + (E)-norgeranylgeranyl diphosphate
show the reaction diagram
geranyl diphosphate + 4 isopentenyl diphosphate
4 diphosphate + all-trans-hexaprenyl diphosphate
show the reaction diagram
geranylgeranyl diphosphate + 2 isopentenyl diphosphate
2 diphosphate + all-trans-hexaprenyl diphosphate
show the reaction diagram
additional information
?
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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
(2E,6E)-farnesyl diphosphate + 3 isopentenyl diphosphate
3 diphosphate + all-trans-hexaprenyl diphosphate
show the reaction diagram
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-Cyclohexanedione
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results in a rapid loss of the component B activity. Component A is resistant, retaining the initial activity almost completely. Farnesyl diphosphate, isopentenyl diphosphate, farnesyl monophosphate and inorganic diphosphate protect the synthase against the inactivation by N-ethylmaleimide, farnesyl diphosphate being the most effective. The presence of Mg2+ is essential for the protection by isopentenyl diphosphate and inorganic diphosphate. For protection of the synthase activity against the inactivation by 2,3-butanedione, the presence of farnesyl diphosphate, isopentenyl diphosphate and Mg2+ is more effective than that of the individual substrates and Mg2+. Inorganic diphosphate provides substantial protection. In the absence of component A, the component B activity is not protected by any substrates or its analogue
2,3-Butanedione
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results in a rapid loss of the component B activity. Component A is resistant, retaining the initial activity almost completely. Farnesyl diphosphate, isopentenyl diphosphate, farnesyl monophosphate and inorganic diphosphate protect the synthase against the inactivation by N-ethylmaleimide, farnesyl diphosphate being the most effective. The presence of Mg2+ is essential for the protection by isopentenyl diphosphate and inorganic diphosphate. For protection of the synthase activity against the inactivation by 2,3-butanedione, the presence of farnesyl diphosphate, isopentenyl diphosphate and Mg2+ is more effective than that of the individual substrates and Mg2+. Inorganic diphosphate provides substantial protection. In the absence of component A, the component B activity is not protected by any substrates or its analogue
7,11-dimethyl-2,6,10-dodecatrien-1-yl diphosphate
O66129 and O66127
analogue of farnesyl diphosphate. Two aspartate-rich motifs and the other characteristic motifs in subunit HexB are located around the diphosphate part of 7,11-dimethyl-2,6,10-dodecatrien-1-yl diphosphate
iodoacetamide
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results in a rapid loss of the component B activity. Component A is resistant, retaining the initial activity almost completely. Farnesyl diphosphate, isopentenyl diphosphate, farnesyl monophosphate and inorganic diphosphate protect the synthase against the inactivation by N-ethylmaleimide, farnesyl diphosphate being the most effective. The presence of Mg2+ is essential for the protection by isopentenyl diphosphate and inorganic diphosphate. For protection of the synthase activity against the inactivation by 2,3-butanedione, the presence of farnesyl diphosphate, isopentenyl diphosphate and Mg2+ is more effective than that of the individual substrates and Mg2+. Inorganic diphosphate provides substantial protection. In the absence of component A, the component B activity is not protected by any substrates or its analogue
N-ethylmaleimide
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results in a rapid loss of the component B activity. Component A is resistant, retaining the initial activity almost completely. Farnesyl diphosphate, isopentenyl diphosphate, farnesyl monophosphate and inorganic diphosphate protect the synthase against the inactivation by N-ethylmaleimide, farnesyl diphosphate being the most effective. The presence of Mg2+ is essential for the protection by isopentenyl diphosphate and inorganic diphosphate. For protection of the synthase activity against the inactivation by 2,3-butanedione, the presence of farnesyl diphosphate, isopentenyl diphosphate and Mg2+ is more effective than that of the individual substrates and Mg2+. Inorganic diphosphate provides substantial protection. In the absence of component A, the component B activity is not protected by any substrates or its analogue
p-chloromercuribenzoate
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results in a rapid loss of the component B activity. Component A is resistant, retaining the initial activity almost completely. Farnesyl diphosphate, isopentenyl diphosphate, farnesyl monophosphate and inorganic diphosphate protect the synthase against the inactivation by N-ethylmaleimide, farnesyl diphosphate being the most effective. The presence of Mg2+ is essential for the protection by isopentenyl diphosphate and inorganic diphosphate. For protection of the synthase activity against the inactivation by 2,3-butanedione, the presence of farnesyl diphosphate, isopentenyl diphosphate and Mg2+ is more effective than that of the individual substrates and Mg2+. Inorganic diphosphate provides substantial protection. In the absence of component A, the component B activity is not protected by any substrates or its analogue
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0067 - 0.0105
(2E,6E)-farnesyl diphosphate
0.0124 - 0.385
geranylgeranyl diphosphate
0.0137 - 0.0216
isopentenyl diphosphate
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20000
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x * 20000 (component A), + x * 60000 (component B), during the course of purification the enzyme is resolved into two components (A and B), each of which has no catalytic activity but restore the hexaprenyl diphosphate synthase activity when combined with each other, gel filtration
50000
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a stable complex of the two essential components of hexaprenyl diphosphate synthase, which represents the catalytically active state of this enzyme, gel filtration
60000
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x * 20000 (component A), + x * 60000 (component B), during the course of purification the enzyme is resolved into two components (A and B), each of which has no catalytic activity but restore the hexaprenyl diphosphate synthase activity when combined with each other, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure both in the substrate-free form and in complex with 7,11-dimethyl-2,6,10-dodecatrien-1-yl diphosphate ammonium salt, an analog of farnesyl diphosphate, to 2.5 A and 2.7 A resolution, respectively. The structure of subunit HexB is composed of mostly antiparallel alpha-helices joined by connecting loops. Two aspartate-rich motifs and the other characteristic motifs in HexB are located around the diphosphate part of 7,11-dimethyl-2,6,10-dodecatrien-1-yl diphosphate. Despite the very low amino acid sequence identity and the distinct polypeptide chain lengths between subunits HexA and HexB, the structure of HexA is quite similar to that of HexB. The aliphatic tail of 7,11-dimethyl-2,6,10-dodecatrien-1-yl diphosphate is accommodated in a large hydrophobic cleft starting from HexB and penetrating to the inside of HexA suggesting that HexB catalyzes the condensation reactions and that HexA is directly involved in the product chain length control in cooperation with HexB
O66129 and O66127
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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component A is more stable against heat treatment than component B. The former retains 75% of its original activity for restoration after a 5 min treatment at 50°C while the latter loses 75% of its activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
during the course of purification the enzyme is resolved into two components (A and B), each of which has no catalytic activity but restore the hexaprenyl pyrophosphate synthetase activity when combined with each other
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purification of component A, purification of component B
O66127 and O66129
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A79F
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mutant enzyme subunit-A(wild-type)/subunit-B(A79L) shows 10fold increased Vmax-values and 11fold decreased Km-values for geranyl diphosphate, which becomes the most preferred substrate of the allylic primers. 5fold increase in KM-value for geranylgeranyl diphosphate. Mutation results in shortening the chain length of the major product. The major products are farnesylgeranyl diphosphate and geranylgeranyl diphosphate
A79L
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mutant enzyme subunit-A(wild-type)/subunit-B(A79L) shows 7fold increased Vmax-values and 6fold decreased Km-values for geranyl diphosphate, which becomes the most preferred substrate of the allylic primers. 3.9fold increase in KM-value for geranylgeranyl diphosphate. Mutation results in shortening the chain length of the major product. The major product is farnesylgeranyl diphosphate
V76G
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mutant enzyme subunit-A(wild-type)/subunit-B(V76G) gives octaprenyl diphosphate as the final products with farnesyl diphosphate as an allylic primer
A79F
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mutant enzyme subunit-A(wild-type)/subunit-B(A79L) shows 10fold increased Vmax-values and 11fold decreased Km-values for geranyl diphosphate, which becomes the most preferred substrate of the allylic primers. 5fold increase in KM-value for geranylgeranyl diphosphate. Mutation results in shortening the chain length of the major product. The major products are farnesylgeranyl diphosphate and geranylgeranyl diphosphate
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A79L
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mutant enzyme subunit-A(wild-type)/subunit-B(A79L) shows 7fold increased Vmax-values and 6fold decreased Km-values for geranyl diphosphate, which becomes the most preferred substrate of the allylic primers. 3.9fold increase in KM-value for geranylgeranyl diphosphate. Mutation results in shortening the chain length of the major product. The major product is farnesylgeranyl diphosphate
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V76G
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mutant enzyme subunit-A(wild-type)/subunit-B(V76G) gives octaprenyl diphosphate as the final products with farnesyl diphosphate as an allylic primer
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additional information