Information on EC 1.13.11.45 - linoleate 11-lipoxygenase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
1.13.11.45
-
RECOMMENDED NAME
GeneOntology No.
linoleate 11-lipoxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
linoleate + O2 = (9Z,12Z)-(11S)-11-hydroperoxyoctadeca-9,12-dienoate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
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-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Linoleic acid metabolism
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SYSTEMATIC NAME
IUBMB Comments
linoleate:oxygen 11S-oxidoreductase
The product (9Z,12Z)-(11S)-11-hydroperoxyoctadeca-9,12-dienoate, is converted, more slowly, into (9Z,11E)-(13R)-13-hydroperoxyoctadeca-9,11-dienoate. The enzyme from the fungus Gaeumannomyces graminis requires Mn2+. It also acts on alpha-linolenate, whereas gamma-linolenate is a poor substrate. Oleate and arachidonate are not substrates.
CAS REGISTRY NUMBER
COMMENTARY hide
9029-60-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
navy bean
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(10Z,13Z,16Z)-nonadeca-10,13,16-trienoic acid + O2
?
show the reaction diagram
-
oxidation at the n-6 carbon and at the bis-allylic position n-8
-
-
?
(11Z,14Z)-eicosadienoic acid + O2
15-hydroxyperoxy-(9Z,11E)-eicosadienoic acid
show the reaction diagram
-
-
-
-
?
(11Z,14Z,17Z)-eicosa-11,14,17-trienoic acid + O2
15-hydroxyperoxy-11Z,13E,17Z-eicosatrienoic acid
show the reaction diagram
-
via 11-hydroperoxyoctadecadienoic acid, 13-hydroperoxyoctadecadienoic acid and 15-hydroperoxyoctadecadienoic acid
-
-
?
(11Z,14Z,17Z)-eicosa-11,14,17-trienoic acid + O2
?
show the reaction diagram
-
oxidation at the n-6 carbon and at the bis-allylic position n-8
-
-
?
(13R)-hydroperoxylinolenic acid + O2
13-ketolinolenic acid + epoxyalcohols
show the reaction diagram
only mutant enzyme G316A
erythro- and threo-11-hydroxy-(12R,13R)-epoxy-(9Z,15Z)-octadecadienoic acids and one of the corresponding cis-epoxides as major products
-
?
(5E,8E,11E,14E)-icosa-5,8,11,14-tetraenoic acid + O2
(5Z,8Z,11S,12E,14Z)-11-hydroperoxyicosa-5,8,12,14-tetraenoic acid + (5Z,8Z,11Z,13E,15R)-15-hydroperoxyicosa-5,8,11,13-tetraenoic acid
show the reaction diagram
-
oxidation at the n-6 carbon and at the bis-allylic position n-8
-
-
?
(5Z,8Z,11Z,14Z,17Z)-docosa-5,8,11,14,17-pentaenoate + O2
?
show the reaction diagram
-
oxidation at the n-6 carbon and at the bis-allylic position n-8
-
-
?
(7Z,10Z,13Z,16Z,19Z)-docosa-7,10,13,16,19-pentaenoate + O2
?
show the reaction diagram
-
oxidation at the n-6 carbon and at the bis-allylic position n-8
-
-
?
(9E,12Z)-octadeca-9,12-dienoic acid + O2
?
show the reaction diagram
-
sLOX-1 oxidizes (9E,12Z)18:2 to 9-hydroperoxyoctadecadienoic acid in an R/S ratio of 60/40 and to 13-hydroperoxyoctadecadienoic acid
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-
?
(9Z,11S,12Z)-11-hydroperoxyoctadeca-9,12-dienoate + O2
(9Z,11E, 13R)-13-hydroperoxyoctadeca-9,11-dienoate
show the reaction diagram
-
-
-
-
?
(9Z,11S,12Z)-11-hydroperoxyoctadeca-9,12-dienoate + O2
(9Z,11E,13R)-13-hydroperoxyoctadeca-9,11-dienoate
show the reaction diagram
-
-
-
-
?
(9Z,12E)-octadeca-9,12-dienoic acid + O2
?
show the reaction diagram
-
sLOX-1 oxidizes (9Z,12E)18:2 slowly to the 9-hydroperoxy metabolite with 10E,12E configuration as the main product (65%) and to 13-hydroperoxyoctadecadienoic acid
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-
?
(9Z,12Z)-octadeca-9,12-dienoic acid + O2
(9S)-hydroperoxy-octadeca-10,12-dienoate
show the reaction diagram
-
alpha-linoleate is converted via two intermediates, (11S)-hydroperoxy-(9Z,12Z)-octadecenoate and (13R)-hydroperoxy-(9Z,11E)-octadecadienoate, which are isomerized to the end product, probably after oxidation to peroxyl radicals, beta-fragmentation, and oxygen insertion at C-9
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-
?
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid + O2
(10E,12E,14E)-9,16-dihydroxy-octadeca-10,12,14-trienoate
show the reaction diagram
-
gamma-linoleate is oxidized at C-9, C-11, and C-13
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-
?
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid + O2
(13R)-hydroperoxyoctadecadienoic acid
show the reaction diagram
-
via bis-allylic 11S-hydroperoxy fatty acid
-
-
?
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid + O2
?
show the reaction diagram
1,2-dilinoleoyl-sn-glycero-3-phosphocholine + O2
?
show the reaction diagram
-
-
main products with 14% and 10%, no production of 11-hydroxyoctadecanoic acid
-
?
1-linoleyl-lyso-glycerophosphatidylcholine + O2
11-hydroxyoctadecanoic acid + 13-hydroxyoctadecanoic acid
show the reaction diagram
-
via formation of the 13-hydroxyperoxy metabolite
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-
?
11-(11R)-hydroperoxy-(9Z,12Z)-octadecadienoic acid
9-(9R)-hydroperoxy-octadecadienoic acid
show the reaction diagram
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slow
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-
?
11-(11S)-hydroperoxy-(9Z,12Z)-octadecadienoic acid
13-(13R)-hydroperoxy-(9Z,11E)-octadecadienoic acid
show the reaction diagram
11-(11S)-hydroperoxy-(9Z,12Z)-octadecadienoic acid methyl ester
13-(13R)-hydroperoxy-(9Z,11E)-octadecadienoic acid methyl ester
show the reaction diagram
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-
-
-
?
11-hydroperoxyoctadecadienoic acid + O2
11,18-dihydroxy-12E,14Z,16E-eicosatrienoic acid
show the reaction diagram
-
-
two diastereoisomers
-
?
alpha-linolenic acid + O2
(13R)-hydroperoxy octadecadienoic acid + 9-hydroperoxyoctadecadienoic acid
show the reaction diagram
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-
-
-
?
alpha-linolenic acid + O2
(9Z,11E,15Z)-(13)-hydroperoxyoctadecatrienoic acid
show the reaction diagram
-
-
-
-
?
alpha-linolenic acid + O2
?
show the reaction diagram
-
-
-
-
?
gamma-linolenic acid + O2
(6Z,9Z,11E)-(13)-hydroperoxyoctadecatrienoic acid + (6Z,9Z,12Z)-(11)-hydroperoxyoctadecatrienoic acid
show the reaction diagram
-
-
-
-
?
linoleate + O2
(9Z,11S,12Z)-11-hydroperoxyoctadeca-9,12-dienoate
show the reaction diagram
-
-
-
-
?
linoleate + O2
(9Z,12Z)-(11S)-11-hydroperoxyoctadeca-9,12-dienoate
show the reaction diagram
linoleic acid + O2
(9Z,11E)-(13R)-hydroperoxyoctadecadienoic acid
show the reaction diagram
linoleic acid + O2
(9Z,11E)-(13R)-hydroperoxyoctadecadienoic acid + (9Z,12Z)-(11S)-hydroperoxyoctadecadienoic acid
show the reaction diagram
-
-
-
ir
linoleic acid + O2
?
show the reaction diagram
-
-
-
-
?
linolenic acid + O2
11-(11S)-hydroperoxy-(9Z,12Z)-octadecadienoic acid
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
(9Z,11S,12Z)-11-hydroperoxyoctadeca-9,12-dienoate + O2
(9Z,11E, 13R)-13-hydroperoxyoctadeca-9,11-dienoate
show the reaction diagram
-
-
-
-
?
linoleate + O2
(9Z,11S,12Z)-11-hydroperoxyoctadeca-9,12-dienoate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
13R-MnLOX forms (11S)-hydroperoxyoctadecadienoic acid and (11R)-hydroperoxyoctadecatrienoic acid as intermediates during the linear phase of oxidation and the (13R)-hydroperoxides as main end products
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
-
non-heme iron
Manganese
-
mononuclear Mn center, 0.94 mol Mn per mol of protein
Mg2+
-
activation less effective than with Ca2+ in phosphate buffer
additional information
-
no activity with Fe3+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
arachidonic acid
-
inhibits at 0.01 mM
eicosatetraynoic acid
N-(3-phenoxycinnamyl) acetohydroxamic acid
0.3 mM, complete inhibition
N-(3-phenoxycinnamyl)acetohydroxamic acid
-
50% of control activity at 0.05 mM
Tween 20
-
inhibition of Ca2+-activated enzyme at pH 7.5 and 6.4, no inhibition at pH 6.4 in the absence of Ca2+
additional information
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no inhibition by lipoxygenase inhibitors zileuton, esculetin and ICI 230487
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
(13R)-hydroperoxylinolenic acid
mutant enzyme G316A
0.0005 - 0.0073
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid
0.0024 - 0.0071
alpha-linolenic acid
0.0044
linoleic acid
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-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
40
alpha-linolenic acid
18.3
linoleic acid
Gaeumannomyces graminis
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-
23.3
O2
Gaeumannomyces graminis
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-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18
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pH 9.0, 21C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.4
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in the absence of Ca2+
7
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broad pH optimum
7.2
-
in the presence of 0.37 mM Ca2+
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 7
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in the absence of Ca2+
4 - 9
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in the presence of 0.37 mM Ca2+
5 - 11
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at pH 5.0 64% of maximum activity, at pH 11 69% of maximum activity
7
-
93% of maximum activity
8
-
98% of maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
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assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12 - 60
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8.8% of maximal activity at 12C and 100% of maximal activity at 60C, activity decreases sharply at 63C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Magnaporthe oryzae (strain 70-15 / ATCC MYA-4617 / FGSC 8958)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
73000
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SDS-PAGE after deglycosylation
135000
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gel filtration with Superdex 200 in 6 M urea
160000
-
gel filtration with Superdex 200
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 80-100000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
63
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incubation for 5 min over 63C decreases activity, no activity at 75C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
9S-LOX activity is less robust during expression and purification, possibly due to proteolysis, stability is not improved by addition of 0.001 mM pepstatin A, 0.001 mM leupeptin, or 1 mM EDTA to the growth medium
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, 3 mM NaN3, 0.2 mM GSH, several months, no loss of activity
-
4C, stable for months
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
phenyl-Sepharose column chromatography
recombinant mini 13R-MnLOX from Pichia pastoris by hydrophobic interaction chromatography and gel filtration
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recombinant wild-type and mutant enzymes from Pichia pastoris by hydrophobic interaction chromatography, dialfiltration, and gel filtration
-
recombinant wild-type and mutant enzymes from Pichia pastoris cell medium by hydrophobic interaction and ion exchange chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
construction, expression, and secretion of truncated 13R-MnLOX, from mini DNA coding for the sequence Glu-Phe-His6-Leu-Gln-Thr39-Val-Leu-Pro to Val618, in Pichia pastoris
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expressed in Pichia pastoris
expression in Pichia pastoris
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expression of wild-type and G316A mutant enzymes in Pichia pastoris strain X-33, secretion to the cell medium
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recombinant expression of wild-type and mutant enzymes in Pichia pastoris
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F337I
-
site-directed mutagenesis, replacement of Phe337 with Ile changes the stereochemistry of the 13-hydroperoxy metabolites of 18:2n-6 and 18:3n-3 (from 100% R to 69-74% S) with little effect on regiospecificity. The abstraction of the pro-S hydrogen of 18:2n-6 is retained, suggesting antarafacial hydrogen abstraction and oxygenation. The mutant shows highly reduced activity compared to the wild-type enzyme
F347A
-
site-directed mutagenesis, the mutant oxidizes octadeca-9,11-dienoic acid to 11-hydroperoxyoctadecadienoate/(13R)-hydroperoxyoctadecadienoate/(9S)-hydroperoxyoctadecadienoate in an initial ratio of 50/42/8 and with almost complete consumption of 11-hydroperoxyoctadecadienoate to a ratio of 2/84/14. The (9E,11Z,15E)-octadeca-9,11,15-trienoic acid is transformed to 11- and (13R)-hydroperoxyoctadecatrienoic acid and to traces of (9S)-hydroperoxyoctadecatrienoic acid, essentially as native 13R-MnLOX
F347L
-
site-directed mutagenesis, (9E,11Z,15E)-octadeca-9,11,15-trienoic acid is oxidized to a 2:3 mixture of (9S)- and (13R)-dihydroxyoctadecatrienoic acid
F347V
-
site-directed mutagenesis
G316T
catalytically inactive
G316V
catalytically inactive
G332A
-
site-directed mutagenesis, replacement of Gly332 with the larger hydrophobic residue selectively augments dehydration of (9Z,11E,13R,15Z)-13-hydroperoxyoctadeca-9,12,15-trienoic acid and increases the oxidation at C-13 of 18:1n-6
H274Q
-
no enzymic activity, loss of more than 95% of manganese content
H278E
-
no enzymic activity, loss of more than 95% of manganese content
H462E
-
no enzymic activity, loss of more than 95% of manganese content
H463Q
-
no significant change in activity
K52N
-
site-directed mutagenesis
L176K
-
site-directed mutagenesis
L336A
-
site-directed mutagenesis, replacement of Leu336 with the smaller hydrophobic residue shifts the oxygenation from C-13 toward C-9 with formation of 9S- and 9R-hydroperoxy metabolites of 18:2n-6 and 18:3n-3, the mutant shows highly reduced activity compared to the wild-type enzyme
L336F
-
site-directed mutagenesis, replacement of Leu336 with the larger hydrophobic residue selectively augments dehydration of (9Z,11E,13R,15Z)-13-hydroperoxyoctadeca-9,12,15-trienoic acid and increases the oxidation at C-13 of 18:1n-6, the mutant shows highly reduced activity compared to the wild-type enzyme
L336G
-
site-directed mutagenesis, replacement of Leu336 with the smaller hydrophobic residue shifts the oxygenation from C-13 toward C-9 with formation of 9S- and 9R-hydroperoxy metabolites of 18:2n-6 and 18:3n-3, the mutant shows highly reduced activity compared to the wild-type enzyme
L336V
-
site-directed mutagenesis, replacement of Leu336 with the smaller hydrophobic residue shifts the oxygenation from C-13 toward C-9 with formation of 9S- and 9R-hydroperoxy metabolites of 18:2n-6 and 18:3n-3, the mutant shows highly reduced activity compared to the wild-type enzyme
N466Q
-
no significant change in activity
Q467N
-
no significant change in activity
S469A
-
site-directed mutagenesis, the mutation hardly affects the bis-allylic hydroperoxide rearrangement, the mutant shows the same substrate profile as the wild-type enzyme
Y158C
-
site-directed mutagenesis
additional information