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Enzyme Nomenclature
Information on EC 4.2.3.129 - (+)-sativene synthase
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EC Tree
4.2.3.129 (+)-sativene synthaseIUBMB Comments
Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-delta-cadinene, beta-copaene, beta-cubebene, and traces of several other sequiterpenoids. See EC 4.2.3.13, (+)-delta-cadinene synthase, EC 4.2.3.127, beta-copaene synthase, and EC 4.2.3.128, beta-cubebene synthase.
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The enzyme appears in viruses and cellular organisms
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Cop4
Cop4
-
-
ambiguous
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(2E,6E)-farnesyl diphosphate = (+)-sativene + diphosphate
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-sativene-forming)
Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-delta-cadinene, beta-copaene, beta-cubebene, and traces of several other sequiterpenoids. See EC 4.2.3.13, (+)-delta-cadinene synthase, EC 4.2.3.127, beta-copaene synthase, and EC 4.2.3.128, beta-cubebene synthase.
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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
(2Z,6E)-farnesyl diphosphate
(+)-sativene + diphosphate
conversion of (E,E)-farnesyl diphosphate proceeds via a (6S)-beta-bisabolene carbocation in the case of Cop4
-
-
?
additional information
?
-
Cop4 cultures produce several sesquiterpene compounds, e.g. beta-cubebene, sativene, beta-copaene, and cubebol
-
-
?
(2E,6E)-farnesyl diphosphate
(+)-sativene + diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate
(+)-sativene + diphosphate
Cop4 synthesizes delta-cadinene as its major product, cf. EC 4.2.3.13
-
-
?
(2E,6E)-farnesyl diphosphate
(+)-sativene + diphosphate
conversion of (E,E)-farnesyl diphosphate proceeds via an (E,E)-germacradienyl carbocation in the case of Cop4
-
-
?
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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
additional information
?
-
Cop4 cultures produce several sesquiterpene compounds, e.g. beta-cubebene, sativene, beta-copaene, and cubebol
-
-
?
(2E,6E)-farnesyl diphosphate
(+)-sativene + diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate
(+)-sativene + diphosphate
Cop4 synthesizes delta-cadinene as its major product, cf. EC 4.2.3.13
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
substitution of Mg2+ with Mn2+ as the divalent metal ion shifts the product profile of Cop4 to germacrene D, disfavoring subsequent ring closures that produce the cadinyl cation and its tricyclic descendents
NaCl
does not affect the product specificity of Cop4 significantly at 1 M
Mg2+
required, substitution of Mg2+ with Mn2+ as the divalent metal ion shifts the product profile of Cop4 to germacrene D, disfavoring subsequent ring closures that produce the cadinyl cation and its tricyclic descendents. Two consensus sequences - an aspartate rich DDXXD/E and a NSE/DTE motif - located at the entrance of the active site coordinate a trinuclear Mg2+ cluster that ligands the diphosphate moiety of the isoprenoid substrate, positions the isoprenyl chain in the binding pocket and triggers closure of the active site along with diphosphate cleavage to generate an initial transoid, allylic carbocation
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
increasing the reaction temperature to 37°C decreases the fidelity of Cop4. At this temperature Cop4 generates a relative larger fraction of products beta-cubebene, sativene, delta-cadinene and beta-copaene, that are derived from a cadinyl cation intermediate
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kinetic analysis, overview
-
0.011
(2E,6E)-farnesyl diphosphate
wild-type enzyme, and mutants H235P and N239L, pH 8.0, 30°
0.048
(2E,6E)-farnesyl diphosphate
Cop6 loop graft mutant Cop6L4, pH 8.0, 30°
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
changing the pH of the reaction drastically alters the fidelity of Cop4 and makes it a highly selective enzyme. Increasing the reaction temperature to 37°C decreases the fidelity of Cop4. At this temperature Cop4 generates a relative larger fraction of products beta-cubebene, sativene, delta-cadinene and beta-copaene, that are derived from a cadinyl cation intermediate. The histidine side chain in the Cop4 loop, in particular, has a strong impact on the net charge of the loop at different pH values
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
identification of constitutive photomorphogenic mutants, cop2, cop3, and cop4,in which dark-grown seedlings have open and enlarged cotyledons resembling those of light-grown wild-type seedlings. Mutations in each of the three loci alleviate the normal inhibition of cell-type differentiation, cell enlargement, and lateral cell division observed in cotyledons of dark-grown wild-type seedlings, but do not affect plastid differentiation. Cop4 mutation also leads to high-leve1 dark expression of nuclear, but not plastid-encoded, light-inducible genes
metabolism
-
epistatic relationships of these three mutations to previously characterized phytochrome-deficient mutations suggest that COP2, COP3, and COP4 may act downstream of phytochrome in the light regulatory pathway
physiological function
additional information
physiological function
-
the COP4 locus may be involved in both light-signaling and gravity-sensing processes. COP4 modulates cabl promoter activity through a pathway distinct from that of COPl and COP9, nuclear cabl gene encodes a chlorophyll alb binding protein of the photosynthetic light-harvesting complex. Modulation of cabl promoter activity by light and by the cop4 mutation
physiological function
the enzyme belongs to the sesquiterpene synthases that are responsible for the cyclization of farnesyl diphosphate into a myriad of structurally diverse compounds with various biological activities
additional information
directed mutations of the H-alpha1 loop have a marked effect on the product profile Cop4, loop mutations in Cop4 also implicate specific residues responsible for the pH sensitivity of the enzyme. In vivo analysis of sesquiterpene product profiles of H-alpha1 loop mutants, overview. Mutation of K233, presumed to interact with the second Asp92 in the DDXXD motif of Cop4, does not significantly change the overall product promiscuity of Cop4, though beta-cubebene, with 27% of total sesquiterpene products, does become the major product
additional information
structural modeling, structure-function relationship, overview. Changing the pH of the reaction drastically alters the fidelity of Cop4 and makes it a highly selective enzyme
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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). COP4_COPC7
Coprinopsis cinerea (strain Okayama-7 / 130 / ATCC MYA-4618 / FGSC 9003)
345
0
39693
Swiss-Prot
other Location (Reliability: 3)
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
structural modeling, structure-function relationship, overview. Cop4 has a large binding pocket in the open conformation
additional information
structure comparison, homology structural modeling of Cop enzymes, overview. Cop4 has a large active site cavity that undergoes substantial conformational change in the model upon ligand binding
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H235P
site-directed mutagenesis, no production of sativene, the mutation converts Cop4 into a much more selective enzyme that produces (-)-germacrene D as the major cyclization product with 50% of total sesquiterpenes products. The mutant makes beta-ylangene, which is a diastereomer of beta-copaene and not synthesized by wild-type Cop4
K233I
site-directed mutagenesis, mutation of K233, interacting with the second Asp92 in the DDXXD motif of Cop4, does not significantly change the overall product promiscuity of Cop4, though beta-cubebene 4 does become the major product and püroduction of sativene is reduced by 50% compared to the wild-type enzyme
N238L
site-directed mutagenesis, the mutant shows a altered product profile compared to the wild-type enzyme with only slight reduction in beta-cubebene synthesis, sativene levels are similar to the wild-type. The mutant does no longer show production of cubebol and has reduced (-)-germacrene D synthesis activity compared to the wild-type enzyme, synthesis of beta-cubebene, beta-copaene, delta-cadinene, and alpha-cubebene
N239L
site-directed mutagenesis, no production of sativene, the mutation converts Cop4 into a much more selective enzyme that produces (-)-germacrene D as the major cyclization product with 50% of total sesquiterpenes products. The mutant makes beta-ylangene, which is a diastereomer of beta-copaene and not synthesized by wild-type Cop4
T236L
site-directed mutagenesis, the mutant shows a altered product profile compared to the wild-type enzyme with an increase in sativene synthesis. The mutant does no longer show production of cubebol and (-)-germacrene D compared to the wild-type enzyme
additional information
additional information
-
generation of a cop4 defective mutant and a cop4/cop1 double mutant
additional information
directed mutations of the H-alpha1 loop have a marked effect on the product profile Cop4, loop mutations in Cop4 also implicate specific residues responsible for the pH sensitivity of the enzyme. H-alpha1 loop swap between Cop4 and Cop6 shifts Cop4 to a germacrene D synthase
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain JM109
gene cop4, DNA and amino acid sequence determination and analysis, phylogenetic analysis, recombinant expression in Escherichia coli strain JM109
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Agger, S.; Lopez-Gallego, F.; Schmidt-Dannert, C.
Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus
Mol. Microbiol.
72
1181-1195
2009
Coprinopsis cinerea (A8NU13), Coprinopsis cinerea ATCC MYA-4618 (A8NU13)
brenda
Lopez-Gallego, F.; Wawrzyn, G.; Schmidt-Dannert, C.
Selectivity of fungal sesquiterpene synthases: Role of the active sites H-1alpha loop in catalysis
Appl. Environ. Microbiol.
76
7723-7733
2010
Coprinopsis cinerea (A8NU13)
brenda
Lopez-Gallego, F.; Agger, S.A.; Abate-Pella, D.; Distefano, M.D.; Schmidt-Dannert, C.
Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers
ChemBioChem
11
1093-1106
2010
Coprinopsis cinerea (A8NU13)
brenda
Hou, Y.; Von Arnim, A.G.; Deng, X.W.
A new class of Arabidopsis constitutive photomorphogenic genes involved in regulating cotyledon development
Plant Cell
5
329-339
1993
Arabidopsis thaliana
brenda
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Release 2023.1 (January 2023)
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