Information on EC 5.4.99.17 - squalene-hopene cyclase

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

EC NUMBER
COMMENTARY
5.4.99.17
-
RECOMMENDED NAME
GeneOntology No.
squalene-hopene cyclase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
squalene + H2O = hopan-22-ol
show the reaction diagram
-
-
-
-
squalene = hop-22(29)-ene
show the reaction diagram
-
-
-
-
squalene = hop-22(29)-ene
show the reaction diagram
catalytic mechanism, the initial reaction catalyzed is the protonation of the terminal double bond of squalene. The conserved DXDD motif of SHCs is essential for this protonation reaction. In Alicyclobacillus acidocaldarius SHC, Asp376 of this motif is hydrogen bonded to His451, and an additional hydrogen bond exists to an ordered water molecule, which connects D376 to the hydroxyl group of the Y495 side chain and thus further enhances its acidity. The carboxyl groups of Asp374 and Asp377 accommodate the positive charge of the D376-H451 pair prior to proton transfer. After proton transfer to the 2,3-double bond of squalene, the D376-H451 pair loses its charge, leaving the remaining negative charge on the D374-D377 pair for stabilization of the initial cationic intermediates (24, 101). Reprotonation of D376 occurs through a water molecule bound to Y495-OH, which can transfer protons from disordered water in the solvent-accessible upper cavity of SHC
-
squalene = hop-22(29)-ene
show the reaction diagram
catalytic mechanism, the initial reaction catalyzed is the protonation of the terminal double bond of squalene. The conserved DXDD motif of SHCs is essential for this protonation reaction, overview
-
squalene = hop-22(29)-ene
show the reaction diagram
catalytic mechanism, overview
-
squalene = hop-22(29)-ene
show the reaction diagram
catalytic mechanism via Friedel-Crafts alkylation and substrate specificity, overview
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cyclization
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
diploterol and cycloartenol biosynthesis
-
hopanoid biosynthesis (bacteria)
-
Sesquiterpenoid and triterpenoid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
squalene mutase (cyclizing)
The enzyme also produces the cyclization product hopan-22-ol by addition of water (cf. EC 4.2.1.129, squalenehopanol cyclase). Hopene and hopanol are formed at a constant ratio of 5:1.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cyclase, squalene-hopanoid
-
-
-
-
SHC
-
-
-
-
SHC
Alicyclobacillus acidocaldarius DSM 446
P33247
-
-
SHC
Q81YD8
-
SHC
Q0B2H5, Q0B5S3
-
SHC
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
-
-
SHC
P73914
-
SHC
P33990
-
SHC
Zymomonas mobilis ZMO-0872
P33990
-
-
SHC
Zymomonas mobilis ZMO-1548
Q5NM88
-
-
SHC1
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B5S3
-
-
SHC2
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5
-
-
Spterp25
B1PT66
-
squalene hopene cyclase
-
-
squalene hopene cyclase
P73914
-
squalene hopene cyclase
Q5NM88
-
squalene-hopene cyclase
-
-
ZmoSHC1
Q5NM88
-
ZmSHC1
Q5NM88
-
CAS REGISTRY NUMBER
COMMENTARY
76600-69-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
YP3187836
GenBank
Manually annotated by BRENDA team
formerly Bacillus acidocaldarius
-
-
Manually annotated by BRENDA team
Alicyclobacillus acidocaldarius 104-IA
strain 104-IA
-
-
Manually annotated by BRENDA team
Alicyclobacillus acidocaldarius DSM 446
-
Uniprot
Manually annotated by BRENDA team
Burkholderia ambifaria ATCC BAA-244/AMMD
-
UniProt
Manually annotated by BRENDA team
Methylococcus capsulatus Bath
strain Bath
-
-
Manually annotated by BRENDA team
gene slr2089
UniProt
Manually annotated by BRENDA team
gene ZMO1548
-
-
Manually annotated by BRENDA team
gene ZMO1548
UniProt
Manually annotated by BRENDA team
Zymomonas mobilis ZMO-0872
-
UniProt
Manually annotated by BRENDA team
Zymomonas mobilis ZMO-1548
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
structure-function relationships of squalene-hopene cyclases, the DXDD motif, which is typical for all squalene-hopene cyclases, overview
evolution
-
squalene hopene cyclases are class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopolycyclic products. The class II mechanism involves the Broensted acid sequence motif DxDD, catalytic mechanism compared to terpene cyclases, overview
malfunction
P73914, -
inactivation of slr2089 leads to accumulation of squalene to a level over 70times higher than in wild-type cells, but no significant growth deficiency in the DELTAshc strain occur compared to the wild-type Synechocystis even at high light conditions
metabolism
-
the enzyme is involved in biosynthesis of hopanoids, members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms
metabolism
-
the nezym eis involved in biosynthesis of hopanoids, members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms
metabolism
-
the enzyme is involved in biosynthesis of hopanoids, members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms
physiological function
-
hopene and hopanol are prokaryotic steroid analogues and have important functions as membrane constituents
metabolism
P73914, -
the enzyme converts squalene into hopene, the substrate for forming hopanoids
additional information
-
structure-function relationships of squalene-hopene cyclases, overview. A large central cavity represents the catalytic site in Alicyclobacillus acidocaldarius enzyme that takes up and orientates the squalene molecule. The channel and active-site cavity inside the protein are separated by a narrow constriction buildup of four amino acids, D376, F166, C435, and F434, that appear to block access to the active site
additional information
-
structure-function relationships of squalene-hopene cyclases, overview
additional information
-
the enzyme catalyzes the cyclization of triterpenoids via cationic intermediates in one of the most complex reactions known in biochemistry
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3S)-2,3-oxidosqualene
lanosterol
show the reaction diagram
-
-
-
-
?
(6E,10E)-2,6,10-trimethyldodeca-2,6,10-triene
(4aR,5S,8aS)-1,1,4a,5,6-pentamethyl-1,2,3,4,4a,5,8,8a-octahydronaphthalene + (4aR,5S,8aS)-1,1,4a,5-tetramethyl-6-methylidenedecahydronaphthalene + (1R,2R,4aS,8aS)-1,2,5,5,8a-pentamethyldecahydronaphthalen-2-ol + (1R,2S,4aS,8aS)-1,2,5,5,8a-pentamethyldecahydronaphthalen-2-ol + (4aS,8aS)-4,4,7,8,8a-pentamethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene + (3S,4aS,8aS)-3,4,4,8,8a-pentamethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene
show the reaction diagram
-
via bicyclic C8-cation
-
-
?
(E,E,E,E)-2,6,10,14,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
8-(4,8-Dimethyl-nona-3,7-dienyl)-1,1,4a,8a-tetramethyl-7-methylene-tetradecahydro-phenanthrene
show the reaction diagram
-
-
low conversion, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
1,1,4a,10a,10b-Pentamethyl-8-methylene-7-(4-methyl-pent-3-enyl)-octadecahydro-chrysene
show the reaction diagram
-
-
one of the three major products, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
1,1,4a,6a,8,10a-Hexamethyl-7-(4-methyl-pent-3-enyl)-1,2,3,4,4a,4b,5,6,6a,7,8,9,10,10a,12,12a-hexadecahydro-chrysene
show the reaction diagram
-
-
one of the three major products, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
1,1,4a,8,10a,10b-Hexamethyl-7-(4-methyl-pent-3-enyl)-1,2,3,4,4a,4b,5,6,8,9,10,10a,10b,11,12,12a-hexadecahydro-chrysene
show the reaction diagram
-
-
one of the three major products, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
2,4a,4b,7,7,10a-Hexamethyl-1-(4-methyl-pent-3-enyl)-octadecahydro-chrysen-2-ol
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
2-(3a,5a,5b,8,8,11a-Hexamethyl-icosahydro-cyclopenta[a]chrysen-3-yl)-propan-2-ol
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
alpha-3-Isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
beta-3-Isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,23-pentamethyltetracosa-2,6,10,14,18,22-hexaene
2-(5a,5b,8,8,11a-Pentamethyl-icosahydro-cyclopenta[a]chrysen-3-yl)-propan-2-ol
show the reaction diagram
-
-
one of the three major products, yield 19.8%, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,23-pentamethyltetracosa-2,6,10,14,18,22-hexaene
3-Isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
one of the three major products, yield 29.4%, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,23-pentamethyltetracosa-2,6,10,14,18,22-hexaene
3-Isopropenyl-5a,5b,8,8,13b-pentamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
one of the three major products, yield 34.8%, NMR spectroscopic analysis
-
?
2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl)phenol
(3S,4aR,6aR,12aR,12bS)-4,4,6a,12b-tetramethyl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H-benzo[a]xanthen-3-ol + (3S,4aR,6aR,12aR,12bS)-4,4,6a,12b-tetramethyl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H-benzo[a]xanthen-3-yl acetate
show the reaction diagram
-
-
-
-
?
2-((2E,6E)-9-(3,3-dimethyloxiran-2-yl)-3,7-dimethylnona-2,6-diethyl)phenol
(4aS,6aR,12aR,12bS)-4,4,6a,12b-tetramethyl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H-benzo[a]xanthene + 2-[[(1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]methyl]phenol + 2-[[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylidenedecahydronaphthalen-1-yl]methyl]phenol
show the reaction diagram
-
-
-
-
?
2-(farnesyldimethylallyl)pyrrole
?
show the reaction diagram
-
-
product is a 10:1 mixture of a tricyclic and a bicyclic unnatural polyprenoid
-
?
3,7,11-trimethyldodeca-1,6,10-trien-3-ol
(-)-caparrapioxide + (-)-8-epi-caparrapioxide
show the reaction diagram
-
-
-
-
-
3-(farnesyldimethylallyl)indole
?
show the reaction diagram
-
-
conversion into a 2:1 mixture of a tetracyclic and a pentacyclic product
-
?
C33 polyprene
?
show the reaction diagram
-
the enzymatic products consist of mono-, bi-, tri-, tetra- and pentacyclic skeletons, however, hexacyclic products are not generated
-
-
?
citronellal
isopulegol
show the reaction diagram
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
P33990, Q5NM88
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
Q5NM88
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
P33990, Q5NM88
activity of mutant F438C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
-
activity of mutant F447C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
Q9X7V9
activity of mutant F449C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
YP3187836
activity of mutant F481C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
-
activity of mutant Y420C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
P33990, Q5NM88
wild-type enzyme, and increased activity in mutant F486C
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
Alicyclobacillus acidocaldarius DSM 446
P33247
activity of mutant Y420C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
Zymomonas mobilis ZMO-0872
P33990
activity of mutant F438C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
Zymomonas mobilis ZMO-1548
Q5NM88
-, wild-type enzyme, and increased activity in mutant F486C
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
compound 5
(-)-caparrapioxide + (-)-8-epi-caparrapioxide
show the reaction diagram
-
-
-
-
?
farnesol
drimenol + albicanol + driman-8,11-diol + [(1S,2R,8aS)-2,5,5,8a-tetramethyl-2-[[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]oxy]decahydronaphthalen-1-yl]methanol
show the reaction diagram
-
-
drimane-type sequiterpenes
-
?
farnesyl phenyl ether
(4aS,5S,8aS)-1,1,4a,6-tetramethyl-5-(phenoxymethyl)-1,2,3,4,4a,5,8,8a-octahydronaphthalene + (4aS,4bR,10bR,12aS)-1,1,4a,10b-tetramethyl-2,3,4,4a,4b,5,10b,11,12,12a-decahydro-1H-naphtho[1,2-c]chromene
show the reaction diagram
-
-
-
-
?
farnesylacetone
sclareoloxide
show the reaction diagram
-
-
-
-
?
geranyl phenyl ether
(6aS,10aS)-7,7,10a-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene
show the reaction diagram
-
-
-
-
?
geranylacetone
(8aS)-2,5,5,8a-tetramethyl-4a,5,6,7,8,8a-hexahydro-4H-chromene
show the reaction diagram
-
-
-
-
?
geranylgeranyl phenyl ether
(14b)-8,13-dimethyl-14-(phenoxymethyl)podocarp-12-ene + (14b)-8-methyl-13-methylidene-14-(phenoxymethyl)podocarpane
show the reaction diagram
-
-
-
-
?
homofarnesoic acid
sclareolide
show the reaction diagram
-
-
-
-
?
homofarnesol
ambroxan
show the reaction diagram
-
-
-
-
?
homofarnesol
ambroxan
show the reaction diagram
Q5NM88
-
-
-
?
homofarnesol
ambroxan
show the reaction diagram
-
-
-
-
?
hongoquercin A
?
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
B1PT66, -
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
P33990, Q5NM88
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
YP3187836
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
A0LJS0
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q81YD8
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q9X7V9
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q0B2H5, Q0B5S3
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
hopanol is also formed
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
the enzyme from Alicyclobacillus acidocaldarius yields pentacyclic hopene and hopanol (diplopterol) via a hopanyl cation from squalene
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
products are formed in a molar ratio of hopene:hopanol, 5:1
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
two types of water molecules ("front water" and "back waters") are involved around the deprotonation site. The two residues of Gln262 and Pro263 probably work to keep away the isopropyl group of the hopanyl cation intermediate from the "front water molecule", that is, to place the "front water" in a favorable position, leading to the minimal production of by-products, i.e., hopanol and hop-21(22)-ene. The five residues of Thr41, Glu45, Glu93, Arg127 and Trp133, by which the hydrogen-bonded network incorporating the "back waters" is constructed, increase the polarization of the "front water" to facilitate proton elimination from the isopropyl moiety of the hopanyl cation, leading to the normal product, hop-22(29)-ene
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Alicyclobacillus acidocaldarius 104-IA
-
products are formed in a molar ratio of hopene:hopanol, 5:1
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Alicyclobacillus acidocaldarius DSM 446
P33247
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-0872
P33990
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-1548
Q5NM88
-
-
-
?
squalene
hopene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
Q5NM88
-
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
the enzyme catalyzes cyclization of the linear triterpenoid squalene to hopene and hopanol by the class II mechanism
-
-
?
hongoquercin B
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
mutations lead to altered product pattern
-
-
-
additional information
?
-
-
overview of cyclization products of wild type and mutant enzymes
-
-
-
additional information
?
-
-
enzyme produces a wide variety of products due to lack of specificity
-
-
-
additional information
?
-
-
(E,E,E,E)-2,6,11,14,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene: no detectable enzymatic activity
-
-
-
additional information
?
-
-
no enzymatic cyclization of 3-(geranylgeranyl)indole
-
-
-
additional information
?
-
-
no substrate: 2-(geranylgeranyl)pyrrole
-
-
-
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
P33990, Q5NM88
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
YP3187836
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
A0LJS0
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q81YD8
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q9X7V9
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q0B2H5, Q0B5S3
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
-
enzyme substrate specificity in polycyclization reactions, overview
-
-
-
additional information
?
-
-
no activity with linalool and pseudoionone
-
-
-
additional information
?
-
-
substrate specificity, detailed overview
-
-
-
additional information
?
-
-
substrate specificity, overview. No activity with prenyl phenyl ether
-
-
-
additional information
?
-
-
the enzyme also catalyzes 2,3-oxidosqualene cyclization, but no tetrahymanol formation. Substrate specificity, detailed overview
-
-
-
additional information
?
-
-
the enzyme also catalyzes 2,3-oxidosqualene cyclization, substrate specificity, detailed overview
-
-
-
additional information
?
-
-
the enzyme does not catalyze 2,3-oxidosqualene cyclization nor tetrahymanol formation. Substrate specificity, detailed overview
-
-
-
additional information
?
-
-
the enzyme does not catalyze tetrahymanol formation. Substrate specificity, detailed overview
-
-
-
additional information
?
-
-
the enzyme shows substrate diversity for polycyclization reactions, since squalene-hopene cyclases specifically address and protonate terminal double bonds of linear terpenoids, molecules with functional groups like carboxylic acids or amides can be used as substrates, overview. It is active with squalene, a C-35 squalene analogue substrate, farnesol, and geranyl geraniol, but not with geraniol, products overview
-
-
-
additional information
?
-
Q5NM88
ZmoSHC1 shows cyclization of the non-natural substrates homofarnesol (C16) and citronellal (C10) in addition to hopene formation from squalene, substrate specificity, overview. ZmoSHC1 exhibits a shift of activity towards substrates of shorter chain lengths, displaying over 50fold higher conversion of homofarnesol and more than 2fold higher conversion of citronellal in comparison to squalene conversion
-
-
-
additional information
?
-
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Alicyclobacillus acidocaldarius DSM 446
P33247
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Zymomonas mobilis ZMO-0872
P33990
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
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
citronellal
isopulegol
show the reaction diagram
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
citronellal
isopulegol
show the reaction diagram
P33990, Q5NM88
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
P33990, Q5NM88
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
YP3187836
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
A0LJS0
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q81YD8
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q9X7V9
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q0B2H5, Q0B5S3
-
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
Q5NM88
-
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Alicyclobacillus acidocaldarius DSM 446
P33247
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-0872
P33990
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-1548
Q5NM88
-
-
-
?
citronellal
isopulegol
show the reaction diagram
Zymomonas mobilis ZMO-1548
Q5NM88
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
P33990, Q5NM88
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
YP3187836
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
A0LJS0
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q81YD8
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q9X7V9
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q0B2H5, Q0B5S3
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Alicyclobacillus acidocaldarius DSM 446
P33247
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Zymomonas mobilis ZMO-0872
P33990
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(18E)-29-methylidenehexanor-2,3-oxidosqualene
-
IC50 0.2 microMol, pH 6.0, 55C
-
(1E,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 1 microMol, pH 6.0, 55C
-
(1E,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.4 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
(1Z,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 4 microMol, pH 6.0, 55C
-
(1Z,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.8 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
(2E)-4-[4-(6-bromo-1,2-benzisothiazol-3-yl)phenoxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[4-[(4-bromophenyl)carbonyl]phenoxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[[3-(4-bromophenyl)-1-benzothiophen-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-phenylthio-1,3,7,11-heptadecatetraene
-
IC50 2.2 microMol, pH 6.0, 55C
-
(4-(2-[(allyl-cyclopropyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 59 nM
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-2-fluoro-phenyl)-methanone
-
IC50 50 nM
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-methanone
-
IC50 62 nM
(4-bromo-phenyl)-(4-[4-(cyclopropyl-methyl-amino)-but-2-enyloxy]-phenyl)-methanone
-
IC50 18 nM
(4-bromo-phenyl)-(4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-methanone
-
IC50 38 nM
(4-chloro-phenyl)-(4-[4-(4,5-dihydro-oxazol-2-yl)-benzylidene]-piperidin-1-yl)-methanone
-
IC50 2800 nM
(4-[6-(allyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 60 nM
(4-[6-(allyl-methyl-amino)-hexyloxy]-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 96 nM
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
i.e. AMO 1618, competitive inhibition
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
99% inhibition at 1 mM
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
-
IC50 7 microMol, pH 6.0, 55C
-
(5E,9E,13E)-17,18-epoxy-5,10,14,18-tetramethyl-1-phenylthio-1,5,9,13-nonadecatetraene
-
IC50 3 microMol, pH 6.0, 55C
-
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
-
IC50 123 nM
1-[(4-chlorophenyl)carbonyl]-4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidine
-
-
1-[4-(trans-4-[[(4-chlorophenoxy)carbonyl](methyl)amino]cyclohexyl)benzyl]piperidinium
-
-
3-(10'-(allylmethylamino)decanoyl)chroman-2,4-dione
-
IC50 100 microMol
-
3-carboxy-4-nitrophenyl-dithio-1,1',2-trisnorsqualene
-
covalently modifies C435
4'-[4-(allyl-methyl-amino)-but-2-enyloxy]-biphenyl-4-yl-(4-bromo-phenyl)-methanone
-
IC50 29 nM
4-chlorophenyl methyl(trans-4-[4-[(1-oxidopiperidin-1-yl)methyl]phenyl]cyclohexyl)carbamate
-
-
4-[4-(allyl-methyl-amino)-but-2-enyloxy]-phenyl-(4-bromo-phenyl)-methanone
-
IC50 40 nM
4-[6-(allyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 1200 nM
4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 760 nM
6-([1-[(4-fluorophenyl)carbonyl]piperidin-4-yl]oxy)-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[(1,3-dimethyl-1H-indazol-5-yl)oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[4-(6-bromo-1,2-benzisothiazol-3-yl)phenoxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[4-[(4-bromophenyl)carbonyl]-3-fluorophenoxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[4-[(4-bromophenyl)carbonyl]phenoxy]-N-(3-hydroxypropyl)-N-methylhexan-1-aminium
-
-
6-[4-[(4-bromophenyl)carbonyl]phenoxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[1-(4-bromophenyl)isoquinolin-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1,2-benzisothiazol-5-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1-methyl-1H-indol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1H-indazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1H-indazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[4-(4-bromophenyl)-1H-2,3-benzoxazin-7-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
7-(10'-(dimethylamino-N-decyloxy))chromen-2-one
-
IC50 5 microMol
-
7-(10-(allylmethylamino)-decyloxy)chromen-2-one
-
IC50 2 microMol
-
7-(4'-(N,N,N'-trimethylethylethylendiamino)-but-2-ynyloxy)chromen-2-one
-
not active at 100 microMol
-
7-(4'-(N-diethylamino)-but-2-ynyloxy)chromen-2-one
-
IC50 5 microMol
-
7-(4'-(N-pyrrolidyn)-but-2-ynyloxy)chromen-2-one
-
IC50 5 microMol
-
7-(4'-allylmethylamino-but-2-ynyloxy)chromen-2-one
-
IC50 0.75 microMol
-
7-(6'-(benzylamino-hexyloxy))chromen-2-one
-
IC50 8 microMol
-
7-(6-(allylmethylamino)-hexyloxy)chromen-2-one
-
IC50 4-5 microMol
-
7-(8'-(dimethylamino-N-octyloxy))chromen-2-one
-
IC50 5-7 microMol
-
7-(morpholinyl-N-hexyloxy)chromen-2-one
-
IC50 6 microMol
-
7-(morpholinyl-N-octyloxy)chromen-2-one
-
IC50 7 microMol
-
7-(piperidinyl-N-hexyloxy)chromen-2-one
-
IC50 8 microMol
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 281 nM; IC50 332 nM
allyl-(4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 23 nM
allyl-(4-[3-(4-bromo-phenyl)-benzo[b]thiophen-6-yloxy]-butyl)-methyl-amine
-
IC50 75 nM
allyl-(4-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-but-2-enyl)-amine
-
IC50 49 nM
allyl-(4-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-but-2-enyl)-methyl-amine
-
IC50 130 nM
allyl-(6-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-hexyl)-methyl-amine
-
IC50 186 nM
allyl-(6-[3-(4-bromo-phenyl)-1-methyl-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 289 nM
allyl-(6-[3-(4-bromo-phenyl)-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 180 nM
allyl-(6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl)-methyl-amine
-
IC50 80 nM
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 306 nM
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 75 nM
allyl-(6-[4-(4-bromo-phenyl)-1H-benzo[d][1,2]oxazin-7-yloxy]-hexyl)-methyl-amine
-
IC50 172 nM
allyl-(6-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-hexyl)-methyl-amine
-
IC50 141 nM
azasqualene
-
inhibition at 0.001 mM
-
Cu2+
-
slight inhibition at 1 mM
diethyldicarbonate
-
92% inhibition at 5 mM
dodecyldimethylamine N-oxide
-
competitive inhibition
dodecyltrimethylammonium bromide
-
competitive inhibition, 50% inhibition at 0.0001 mM
Farnesol
-
inhibition at 0.1 mM
Fe2+
-
slight inhibition at 1 mM
HECAMEG
-
80% inactivation compared to CHAPS
N,N-dimethyldodecylamine N-oxide
-
forms a complex with the enzyme
N-(6-[4-[(4-bromophenyl)carbonyl]-3-fluorophenoxy]hexyl)-N-methylcyclopropanaminium
-
-
N-([4'-[(4-bromophenyl)carbonyl]biphenyl-4-yl]methyl)-N-methylprop-2-en-1-aminium
-
-
N-dodecyliodoacetamide
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant >200 microMol, pH 6.0, 50C
-
N-ethylmaleimide
-
65% inhibition at 5 mM, 20% inhibition at 1 mM
N-squalenyliodoacetamide
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant 50 microMol, pH 6.0, 50C
-
N-[(2E)-4-[4-[(4-bromophenyl)carbonyl]phenoxy]but-2-en-1-yl]-N-methylcyclopropanaminium
-
-
N-[6-([1-[(4-fluorophenyl)carbonyl]piperidin-4-yl]oxy)hexyl]-N-methylcyclopropanaminium
-
-
N-[[(1S,2S)-2-([4-[(4-bromophenyl)carbonyl]-3-fluorophenoxy]methyl)cyclopropyl]methyl]-N-methylcyclopropanaminium
-
-
N-[[(1S,2S)-2-([4-[(4-bromophenyl)carbonyl]phenoxy]methyl)cyclopropyl]methyl]-N-methylcyclopropanaminium
-
-
N-[[(1S,2S)-2-([4-[(4-bromophenyl)carbonyl]phenoxy]methyl)cyclopropyl]methyl]-N-prop-2-en-1-ylcyclopropanaminium
-
-
octylthiogucopyranoside
-
complete inactivation
p-chloromercuribenzenesulfonic acid
-
96% inhibition at 1 mM
Ro 48-8071
-
IC50 0.35 microMol
sodium dodecylsulfate
-
strong inhibition
sodium taurodeoxycholate
-
under 0.15% and above 0.25%
squalene-maleimide
-
time-dependent inhibitor
taurodeoxycholate
-
80% inactivation compared to CHAPS
Triton-X100
-
96% inhibition
Zn2+
-
slight inhibition at 5 mM
Zwittergent
-
80% inactivation compared to CHAPS
-
methyl-[4-(4-piperidin-1-ylmethyl-phenyl)-cyclohexyl]-carbamic acid 4-chloro-phenyl ester
-
IC50 406 nM
additional information
-
vinyl sulfide and ketene dithioacetal derivates of truncated 2,3-ocidosqualene interact with active site of the enzyme
-
additional information
-
sulfur-substituted oxidosqualene analogues serve as inhibitors
-
additional information
-
effect of thiol-modifying inhibitors on mutant enzymes
-
additional information
-
inhibition by n-alkyldimethylammoniumhalides with alkyl chain lengths between 12 and 18 C atoms, inhibition increases with decreasing chain length
-
additional information
-
several detergents have inhibitory effect
-
additional information
-
sulfur-containing analogues of 2,3-oxidosqualene inhibit enzyme activity, 50% inhibition at concentrations in the nanomolar range
-
additional information
-
inhibitors designed as cholesterol-lowering agents, for 11 inhibitors the structures of the enzyme-inhibitor complexes were determined by X-ray crystallography
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ethanol
-
1.6fold increase of activity when added to the enzyme test system at a concentration of 6%
Propanol
-
1.6fold increase of activity when added to the enzyme test system at a concentration of 6%
sodium taurodeoxycholate
-
1.5fold activation at 0.16%
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.001
-
(3S)-2,3-oxidosqualene
-
quintuple mutant, 50C, pH 6.0
0.0015
-
(3S)-2,3-oxidosqualene
-
wild-type, 50C, pH 6.0
0.01
-
squalene
-
quintuple mutant, 50C, pH 6.0
0.0132
-
squalene
-
wild-type, 50C, pH 6.0
0.0154
-
squalene
-
wild-type, pH 6.0, 40C
0.0162
-
squalene
-
pH 6.0, 45C, wild-type enzyme; wild-type, 45C, pH 6.0
0.0167
-
squalene
-
mutant T41A, 45C, pH 6.0; pH 6.0, 45C, mutant T41A
0.0169
-
squalene
-
mutant W133A, 45C, pH 6.0; pH 6.0, 45C, mutant W133A
0.017
-
squalene
-
wild type enzyme and D376E mutant
0.0189
-
squalene
-
mutant E93A, 45C, pH 6.0; pH 6.0, 45C, mutant E93A
0.0213
-
squalene
-
mutant E45A, 45C, pH 6.0; pH 6.0, 45C, mutant E45A
0.0242
-
squalene
-
wild-type, pH 6.0, 50C
0.0255
-
squalene
-
mutant R127Q, 45C, pH 6.0; pH 6.0, 45C, mutant R127Q
0.0279
-
squalene
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.0324
-
squalene
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.0352
-
squalene
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50C
0.0416
-
squalene
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50C
0.0479
-
squalene
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50C
0.0525
-
squalene
-
mutant F605Y, pH 6.0, 40C
0.0816
-
squalene
-
pH 6.0, 45C, mutant F434A
0.0955
-
squalene
-
pH 6.0, 45C, mutant F437A
0.102
-
squalene
-
mutant Q262A, 45C, pH 6.0; pH 6.0, 45C, mutant Q262A
0.104
-
squalene
-
mutant F605Y, pH 6.0, 50C
0.105
-
squalene
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40C
0.118
-
squalene
-
mutant F605W, pH 6.0, 40C
0.13
-
squalene
-
mutant F365Y, pH 6.0, 50C
0.152
-
squalene
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50C
0.156
-
squalene
-
mutant Q262G, 45C, pH 6.0; pH 6.0, 45C, mutant Q262G
0.185
-
squalene
-
mutant P263A, 45C, pH 6.0; pH 6.0, 45C, mutant P263A
0.185
-
squalene
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50C
0.191
-
squalene
-
mutant F605W, pH 6.0, 50C
0.197
-
squalene
-
mutantY267A, 45C, pH 6.0; pH 6.0, 45C, mutant Y267A
0.237
-
squalene
-
mutant P263G, 45C, pH 6.0; pH 6.0, 45C, mutant P263G
0.816
-
squalene
-
mutant F434A, 45C, pH 6.0
0.955
-
squalene
-
mutant F437A, 45C, pH 6.0
0.0023
-
(3S)-2,3-oxidosqualene
-
sextuple mutant, 50C, pH 6.0
additional information
-
additional information
-
Km for wild type and mutant enzymes
-
additional information
-
additional information
-
squalene sextuple mutant: no activity
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.15
-
squalene
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50C
0.17
-
squalene
-
mutant F365Y, pH 6.0, 50C
0.25
-
squalene
-
wild-type, pH 6.0, 40C
0.27
-
squalene
-
mutant F605Y, pH 6.0, 40C
0.31
-
squalene
-
mutant F605W, pH 6.0, 40C
0.345
-
squalene
-
pH 6.0, 45C, mutant E45A
0.353
-
squalene
-
pH 6.0, 45C, mutant E93A
0.448
-
squalene
-
pH 6.0, 45C, mutant R127Q
0.45
-
squalene
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40C
0.54
-
squalene
-
pH 6.0, 45C, mutant F434A
0.54
-
squalene
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.62
-
squalene
-
pH 6.0, 45C, mutant W133A
0.64
-
squalene
-
pH 6.0, 45C, mutant Y267A
0.7
-
squalene
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50C
0.735
-
squalene
-
pH 6.0, 45C, mutant T41A
0.75
-
squalene
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50C
0.82
-
squalene
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.86
-
squalene
-
pH 6.0, 45C, wild-type enzyme
0.92
-
squalene
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50C
1.03
-
squalene
-
pH 6.0, 45C, mutant F437A
1.06
-
squalene
-
pH 6.0, 45C, mutant P263G
1.09
-
squalene
-
pH 6.0, 45C, mutant P263A
1.1
-
squalene
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50C
1.21
-
squalene
-
pH 6.0, 45C, mutant Q262A
1.32
-
squalene
-
mutant F605W, pH 6.0, 50C
1.37
-
squalene
-
pH 6.0, 45C, mutant Q262G
1.82
-
squalene
-
mutant F605Y, pH 6.0, 50C
1.98
-
squalene
-
wild-type, pH 6.0, 50C
additional information
-
additional information
-
wild type and mutant enzymes
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.2
-
squalene
-
pH 6.0, 45C, mutant Y267A
496
4.5
-
squalene
-
pH 6.0, 45C, mutant P263G
496
5.9
-
squalene
-
pH 6.0, 45C, mutant P263A
496
6.6
-
squalene
-
pH 6.0, 45C, mutant F434A
496
8.8
-
squalene
-
pH 6.0, 45C, mutant Q262G
496
10.8
-
squalene
-
pH 6.0, 45C, mutant F437A
496
11.9
-
squalene
-
pH 6.0, 45C, mutant Q262A
496
16.1
-
squalene
-
pH 6.0, 45C, mutant E45A
496
17.6
-
squalene
-
pH 6.0, 45C, mutant R127Q
496
18.7
-
squalene
-
pH 6.0, 45C, mutant E93A
496
36.7
-
squalene
-
pH 6.0, 45C, mutant W133A
496
44
-
squalene
-
pH 6.0, 45C, mutant T41A
496
53.09
-
squalene
-
pH 6.0, 45C, wild-type enzyme
496
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00054
-
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
-
0.00014
-
dodecyldimethylamine N-oxide
-
-
0.00032
-
dodecyltrimethylammonium bromide
-
-
additional information
-
additional information
-
Ki for sulfur-substituted oxidosqualene analogues
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0002
-
(18E)-29-methylidenehexanor-2,3-oxidosqualene
-
IC50 0.2 microMol, pH 6.0, 55C
-
0.001
-
(1E,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 1 microMol, pH 6.0, 55C
-
0.0014
-
(1E,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.4 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
0.004
-
(1Z,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 4 microMol, pH 6.0, 55C
-
0.0018
-
(1Z,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.8 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
0.0022
-
(3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-phenylthio-1,3,7,11-heptadecatetraene
-
IC50 2.2 microMol, pH 6.0, 55C
-
0.000059
-
(4-(2-[(allyl-cyclopropyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 59 nM
0.00005
-
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-2-fluoro-phenyl)-methanone
-
IC50 50 nM
0.000062
-
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-methanone
-
IC50 62 nM
0.000018
-
(4-bromo-phenyl)-(4-[4-(cyclopropyl-methyl-amino)-but-2-enyloxy]-phenyl)-methanone
-
IC50 18 nM
0.000038
-
(4-bromo-phenyl)-(4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-methanone
-
IC50 38 nM
0.0028
-
(4-chloro-phenyl)-(4-[4-(4,5-dihydro-oxazol-2-yl)-benzylidene]-piperidin-1-yl)-methanone
-
IC50 2800 nM
0.00006
-
(4-[6-(allyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 60 nM
0.000096
-
(4-[6-(allyl-methyl-amino)-hexyloxy]-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 96 nM
0.007
-
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
-
IC50 7 microMol, pH 6.0, 55C
-
0.003
-
(5E,9E,13E)-17,18-epoxy-5,10,14,18-tetramethyl-1-phenylthio-1,5,9,13-nonadecatetraene
-
IC50 3 microMol, pH 6.0, 55C
-
0.000123
-
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
-
IC50 123 nM
0.1
-
3-(10'-(allylmethylamino)decanoyl)chroman-2,4-dione
-
IC50 100 microMol
-
0.000029
-
4'-[4-(allyl-methyl-amino)-but-2-enyloxy]-biphenyl-4-yl-(4-bromo-phenyl)-methanone
-
IC50 29 nM
0.00004
-
4-[4-(allyl-methyl-amino)-but-2-enyloxy]-phenyl-(4-bromo-phenyl)-methanone
-
IC50 40 nM
0.0012
-
4-[6-(allyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 1200 nM
0.00076
-
4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 760 nM
0.000075
-
6-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
0.005
-
7-(10'-(dimethylamino-N-decyloxy))chromen-2-one
-
IC50 5 microMol
-
0.002
-
7-(10-(allylmethylamino)-decyloxy)chromen-2-one
-
IC50 2 microMol
-
0.005
-
7-(4'-(N-diethylamino)-but-2-ynyloxy)chromen-2-one, 7-(4'-(N-pyrrolidyn)-but-2-ynyloxy)chromen-2-one
-
IC50 5 microMol
-
0.00075
-
7-(4'-allylmethylamino-but-2-ynyloxy)chromen-2-one
-
IC50 0.75 microMol
-
0.008
-
7-(6'-(benzylamino-hexyloxy))chromen-2-one
-
IC50 8 microMol
-
0.004
0.005
7-(6-(allylmethylamino)-hexyloxy)chromen-2-one
-
IC50 4-5 microMol
-
0.005
0.007
7-(8'-(dimethylamino-N-octyloxy))chromen-2-one
-
IC50 5-7 microMol
-
0.006
-
7-(morpholinyl-N-hexyloxy)chromen-2-one
-
IC50 6 microMol
-
0.007
-
7-(morpholinyl-N-octyloxy)chromen-2-one
-
IC50 7 microMol
-
0.008
-
7-(piperidinyl-N-hexyloxy)chromen-2-one
-
IC50 8 microMol
-
0.000281
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 281 nM
0.000332
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 332 nM
0.000023
-
allyl-(4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 23 nM
0.000075
-
allyl-(4-[3-(4-bromo-phenyl)-benzo[b]thiophen-6-yloxy]-butyl)-methyl-amine
-
IC50 75 nM
0.000049
-
allyl-(4-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-but-2-enyl)-amine
-
IC50 49 nM
0.00013
-
allyl-(4-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-but-2-enyl)-methyl-amine
-
IC50 130 nM
0.000186
-
allyl-(6-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-hexyl)-methyl-amine
-
IC50 186 nM
0.000289
-
allyl-(6-[3-(4-bromo-phenyl)-1-methyl-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 289 nM
0.00018
-
allyl-(6-[3-(4-bromo-phenyl)-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 180 nM
0.00008
-
allyl-(6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl)-methyl-amine
-
IC50 80 nM
0.000306
-
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 306 nM
0.000075
-
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 75 nM
0.000172
-
allyl-(6-[4-(4-bromo-phenyl)-1H-benzo[d][1,2]oxazin-7-yloxy]-hexyl)-methyl-amine
-
IC50 172 nM
0.000141
-
allyl-(6-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-hexyl)-methyl-amine
-
IC50 141 nM
0.000406
-
methyl-[4-(4-piperidin-1-ylmethyl-phenyl)-cyclohexyl]-carbamic acid 4-chloro-phenyl ester
-
IC50 406 nM
0.2
-
N-dodecyliodoacetamide
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant >200 microMol, pH 6.0, 50C
-
0.05
-
N-squalenyliodoacetamide
-
IC50 sextuple mutant 50 microMol, pH 6.0, 50C
-
0.2
-
N-squalenyliodoacetamide
-
IC50 quintuple mutant >200 microMol; IC50 wild-type >200 microMol
-
0.00035
-
Ro 48-8071
-
IC50 0.35 microMol
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00000227
-
-
crude extract
additional information
-
-
specific activities for wild type and mutant enzymes
additional information
-
-
enzyme activities in mg/ml of product with different substrates and at different enzyme concentrations, overview
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.8
8
-
50% activity at pH 8, very low activity at pH 4.8
5
8
-
no activity below pH 5 or above pH 8
5
8
-
activity range
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
45
B1PT66, -
at pH 6.8
45
-
-
mutant F437A; mutant F437A0
50
60
-
mutantY267A; mutant Y267A
50
-
-
mutant E45A; mutant P263A; mutant P263G; mutant P263G, mutant P263A, mutant E45A, mutant R127Q; mutant R127Q
55
-
-
mutant E93A; mutant E93A, mutant W133A; mutant W133A
60
-
-
mutant F434A; mutant T41A; wild-type; wild-type, mutant T41A, mutant F434A
additional information
-
-
wild type and mutant enzymes
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Alicyclobacillus acidocaldarius 104-IA, Methylococcus capsulatus Bath
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
70000
-
-
SDS-PAGE
74000
-
-
calculated from amino acid sequence
92000
-
B1PT66, -
recombinant His-tagged Spterp25, SDS-PAGE
150000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 71600, SDS-PAGE
?
-
x * 76300, SDS-PAGE
?
-
x * 74100, SDS-PAGE
?
-
x * 72300, SDS-PAGE
?
-
x * 74100, SDS-PAGE
?
-
x * 72000, SDS-PAGE
?
-
x * 74100, SDS-PAGE
dimer
-
2 * 75000, SDS-PAGE, enzyme forms aggregates in absence of detergent
additional information
-
dumbbell-shaped structure of chain A with a more structured beta-barrel structure in domain 1, active site structure, structure analysis, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cocrystallization with 2-azasqualene
-
complexes with 11 human oxidosqualene cyclase inhibitors produced by cocrystallization, elucidation of the structures by X-ray diffraction analyses
-
resolution of 2.0 Angstrom
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
60
-
-
wild type enzyme: 50% loss of activity after 120 min, D376E mutant: 50% loss of activity after 100 min
70
-
-
stable for 10 min
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, stable for weeks
-
6C, stable for several days
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ion exchange and gel filtration
-
wild type and mutants, homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli BL21
-
expression in Escherichia coli JM 105
-
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
expressed in Escherichia coli BL21(DE3)pLysS cells
B1PT66, -
gene slr2089, DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
P73914, -
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
gene ZMO1548, genetic organization
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
F481C
YP3187836
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
C25S/C50S/C435S/C455S/C537S
-
quintuple mutant
C25S/C50S/D376C/C435S/C455S/C537S
-
sextuple mutant
C435S/D374I/D374V/H451F
-
inactive mutant
D376E
-
10% enzyme activity
D376E
-
inactive mutant
D376E/D377E
-
no enzyme activity
D376G
-
0.2% activity when enzyme concentration is increased to 100fold
D376Q
-
no enzyme activity
D376R
-
no enzyme activity
D377C/D377N/Y612A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
D377C/V380E/V381A
-
no detectable cyclization of squalene
D377E
-
0.2% activity when enzyme concentration is increased to 100fold
D377E/D376Q/D376R/D377R/E45K/W406V/W417A/D377C
-
inactive mutant
D377G
-
0.2% activity when enzyme concentration is increased to 100fold
D377Q
-
0.2% activity when enzyme concentration is increased to 100fold
D377R
-
no enzyme activity
E45A
-
reduced enzyme activity
E45A
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
E45D
-
reduced enzyme activity
E45K
-
no enzyme activity
E45Q
-
slightly increased enzyme activity
E93A
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
F365A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F365W
-
marginal catalytic activity
F365Y
-
and mutant with F365 changed to unnatural amino acid O-methyltyrosine. Both show increased decreased activity at high temperature
F434A
-
mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
F437A
-
mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
F601A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F605A
-
altered product pattern
F605A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F605W
-
increased catalytic acitivy at low temperature, but decreased activity at high temperature due to higher cation-pi binding energies
F605Y
-
and mutant with F605 changed to unnatural amino acid O-methyltyrosine. Both show increased catalytic acitivy at low temperature, but decreased activity at high temperature due to higher cation-pi binding energies
G262A
-
the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
P263A
-
mutation located between C29 of the hopanyl cation and the 'front water'; the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
P263G
-
mutation located between C29 of the hopanyl cation and the 'front water'; the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
Q262A
-
mutation located between C29 of the hopanyl cation and the 'front water'
Q262G
-
mutation located between C29 of the hopanyl cation and the 'front water'; the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
Q262G/Q262A/P263G/P263A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
R127Q
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
T41A
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
V380E
-
inactive mutant
V381A/D376C
-
inactive mutant
W133A
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
W169F/W169H/W489A/F605K
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
W23V
-
same activity and optimal temperature as wild type enzyme
W258L
-
60% of wild type activity, lower temperature optimum
W406V
-
no enzyme activity
W417A
-
no enzyme activity
W485V
-
same activity and optimal temperature as wild type enzyme
W522V
-
same activity and optimal temperature as wild type enzyme
W533A
-
same activity and optimal temperature as wild type enzyme
W591L
-
same activity and optimal temperature as wild type enzyme
W78S
-
same activity and optimal temperature as wild type enzyme
Y267A
-
mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
Y420A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y420C
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
Y495F
-
reduced enzyme activity, wild-type product pattern
Y606A
-
kinetics identical to wild-type
Y606A/W23V/W495V/W522V/W533A/W591L/W78S/E35Q/E197Q/D530N/T378A
-
the mutant shows the same product pattern and activity as the wild-type
Y609A/Y612A/L607K
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y609F
-
wild type activity, altered product pattern
Y609F
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y612F
-
reduced enzyme activity, wild-type product pattern
Y612F/D376E/D376G/D377E/D377G/D377Q/E45A/E45D/F365W/T41A/E93A/R127Q/W133A/Y267A/F434A/F437A/W258L/D350N/D421N/D442N/H451R/D447N/D377N/D313N/E535Q/D374E
-
the mutant shows the same product pattern as the wild-type with less enzyme activity
Y420C
Alicyclobacillus acidocaldarius DSM 446
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
-
F409C
Q81YD8
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F447C
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
F436C
Q0B2H5, Q0B5S3
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F450C
Q0B2H5, Q0B5S3
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F436C
Burkholderia ambifaria ATCC BAA-244/AMMD
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
-
F450C
Burkholderia ambifaria ATCC BAA-244/AMMD
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
-
F445C
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F457C
A0LJS0
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F438C
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F438C
P33990, Q5NM88
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
F486C
P33990, Q5NM88
site-directed mutagenesis, the mutant shows increased activity in interconversion of citronellal and isopulegol compared to the wild-type enzyme
W555A
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555C
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555D
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and moderate citronellal cyclase activity
W555E
P33990, Q5NM88
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and low citronellal cyclase activity
W555F
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
W555G
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555H
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and moderate citronellal cyclase activity
W555I
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555K
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555L
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555M
P33990, Q5NM88
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and low citronellal cyclase activity
W555N
P33990, Q5NM88
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and moderate citronellal cyclase activity
W555P
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555Q
P33990, Q5NM88
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and low citronellal cyclase activity
W555R
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555S
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555T
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and higher citronellal cyclase activity
W555V
P33990, Q5NM88
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555Y
P33990, Q5NM88
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity,and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
F438C
Zymomonas mobilis ZMO-0872
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
-
F486C
Zymomonas mobilis ZMO-1548
-
site-directed mutagenesis, the mutant shows increased activity in interconversion of citronellal and isopulegol compared to the wild-type enzyme
-
W555F
Zymomonas mobilis ZMO-1548
-
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
-
W555Y
Zymomonas mobilis ZMO-1548
-
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity,and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
-
I261A
-
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
additional information
-
mutations of Y609, Y495, Y612 and Y420 lead to an altered product pattern, compared to wild-type enzyme
additional information
-
overview
additional information
-
modification of critically located Cys residues
additional information
-
various mutations of conserved amino acid residues
additional information
-
replacement of F605 by mono-, di- or trifluorophenylalanine, with or without additional mutation Y606A, kinetic analysis. Mutant F605 changed to trifluorophenylalanine plus mutation Y606A has negligibly small activity
additional information
-
product patterns of mutant enzymes, detailed overview
F438C
Q9X7V9
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
additional information
P73914, -
knockout of gene slr2089, phenotype and self-complementation by gene slr2089 expression
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
synthesis
-
production of unnatural polyprenoids and supranatural steroids by manipulation of the enzyme reaction by combination of substrate analogues
synthesis
P73914, -
it is possible to use the cyanobacterium Synechocystis to generate squalene, a hydrocarbon of commercial interest and a potential biofuel
synthesis
-
cyclization of homofarnesol to ambroxan as well as the conversion of citronellal to 2-isopropenyl-5-methyl-cyclohexanol bythe isozyme SHC1 can be economically attractive, as both products are used in the flavour and fragrance industry