1.13.11.31: arachidonate 12-lipoxygenase
This is an abbreviated version!
For detailed information about arachidonate 12-lipoxygenase, go to the full flat file.
Word Map on EC 1.13.11.31
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1.13.11.31
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arachidonic
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cyclooxygenase
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12-hete
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eicosanoids
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prostaglandin
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endothelial
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phospholipase
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neutrophil
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atherosclerosis
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polyunsaturated
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linoleic
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artery
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baicalein
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lipoxins
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hetes
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monocyte
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12-hydroxyeicosatetraenoic
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cox-2
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reticulocyte
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asthma
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nordihydroguaiaretic
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thromboxane
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eicosapentaenoic
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hydroperoxide
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ndga
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polymorphonuclear
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atherogenesis
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docosahexaenoic
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indomethacin
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5,8,11,14-eicosatetraynoic
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etya
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zileuton
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13-hode
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hydroperoxy
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lipoxygenase-1
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erythroderma
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hydroxyeicosatetraenoic
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medicine
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esculetin
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protectins
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ichthyosiform
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resolvins
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polyenoic
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pro-resolving
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drug development
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14carachidonic
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ichthyosis
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ferroptosis
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5-lipoxygenase-activating
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phenidone
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a23187-stimulated
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oxylipins
- 1.13.11.31
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arachidonic
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cyclooxygenase
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12-hete
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eicosanoids
- prostaglandin
- endothelial
- phospholipase
- neutrophil
- atherosclerosis
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polyunsaturated
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linoleic
- artery
- baicalein
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lipoxins
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hetes
- monocyte
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12-hydroxyeicosatetraenoic
- cox-2
- reticulocyte
- asthma
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nordihydroguaiaretic
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thromboxane
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eicosapentaenoic
- hydroperoxide
- ndga
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polymorphonuclear
- atherogenesis
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docosahexaenoic
- indomethacin
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5,8,11,14-eicosatetraynoic
- etya
- zileuton
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13-hode
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hydroperoxy
- lipoxygenase-1
- erythroderma
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hydroxyeicosatetraenoic
- medicine
- esculetin
-
protectins
-
ichthyosiform
-
resolvins
-
polyenoic
-
pro-resolving
- drug development
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14carachidonic
- ichthyosis
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ferroptosis
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5-lipoxygenase-activating
- phenidone
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a23187-stimulated
- oxylipins
Reaction
Synonyms
(12R)-lipoxygenase, (12R)-LOX, 11R-lipoxygenase, 11R-LOX, 12(R)-lipoxygenase, 12(S)-lipoxygenase, 12-hLO, 12-lipoxygenase, 12-LO, 12-LOX, 12/15 lipoxygenase, 12/15 Lox, 12/15-lipoxygenase, 12/15-lipoxygenases, 12/15-LO, 12/15-LOX, 12/15LO, 12DELTA-lipoxygenase, 12LO, 12R-lipoxygenase, 12R-LOX, 12R-LOX-2, 12S-lipoxygenase, 15-lipoxygenase, 15-LO, 15-LOX-1, 2-lipoxygenase, 2/15-lipoxygenase, ALOX 12, ALOX 12/15, ALOX12, Alox12b, Alox12e, Alox15, ALOX15B, ALOX5, arachidonate 12/15-lipoxygenase, C-12 lipoxygenase, cardiac 12/15-LOX, DELTA 12-lipoxygenase, epidermal-type lipoxygenase, hp-12LOX, human platelet 12-lipoxygenase, leukocyte-type 12-lipoxygenase, leukocyte-type 12-LOX, leukocyte-type 12/15-lipoxygenase, leukocyte-type lipoxygenase, leukotriene A4 synthase M, lipoxygenase 12, LOX, LOX-12, LOX1, LTA4 synthase, oxylipin-producing enzyme, oygenase, arachidonate 12-lip-, P-12LOX, p12-LO, p12-LOX, platelet 12-lipoxygenase, platelet-type 12(S)-lipoxygenase, platelet-type 12-human lipoxygenase, platelet-type 12-lipoxygenase, platelet-type 12-LOX, platelet-type 12LO, Platelet-type lipoxygenase 12, WP_046712474, zf12-LOX
ECTree
1.13.11.31 arachidonate 12-lipoxygenaseAdvanced search results
results (
results (Engineering
Engineering on EC 1.13.11.31 - arachidonate 12-lipoxygenase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C7S
site-directed mutagenesis, the mutant shows highly reduced iron content compared to the wild-type enzyme, but exchange of the surface-exposed cysteine alters neither the catalytic activity nor the reaction specificity
F174A/W176A/L183E/L187E/Y191A
quintuple mutant disrupts both the hydrophobic and pi-pi interactions of the dimer interface, generating an 12-LOX monomer
G441A
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the mutant enzyme G441A converts arachidonic acid to (8S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid and (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid in a 1.4:1 ratio, wild-type enzyme converts arachidonate only to (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid
G441S
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the mutant enzyme G441A converts arachidonic acid to 8S-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (major product) and (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (minor product), wild-type enzyme converts arachidonate only to (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid
I417A
naturally occuring mutation, the mutant produces 94% 12-hydroperoxyicosatetraenoate and 6% 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces 15% 12-hydroperoxyicosatetraenoate and 85% 15-hydroperoxyicosatetraenoate
L183E/L187E
mutant mostly forms monomers, product ratio of 12S:15S-enantiomer is 78:22, strong decrease in inhibition by ML355
M419T
naturally occuring mutation, the mutant produces more 12-hydroperoxyicosatetraenoate compared to 15-hydroperoxyicosatetraenoate, incontrast to the wild-type, inversed substrate specificity
T560M
T594V
naturally occuring mutation, the mutant produces more 12-hydroperoxyicosatetraenoate compared to 15-hydroperoxyicosatetraenoate, incontrast to the wild-type, inversed substrate specificity
Q303L
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mutant shows strongly impared catalytic activity, relative catalytic activity: 3.2% compared to wild-type 100%
T570M
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mutant shows strongly impared catalytic activity, relative catalytic activity: 8.2% compared to wild-type 100%
W633X
I418A
naturally occuring mutation, the mutant produces exclusively 12-hydroperoxyicosatetraenoate and almost no 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces about equal amounts of both
I418F
naturally occuring mutation, the mutant produces more 15-hydroperoxyicosatetraenoate compared to 12-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces about equal amounts of both
I418A
naturally occuring mutation, the mutant produces 92% 12-hydroperoxyicosatetraenoate and 8% 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces 3% 12-hydroperoxyicosatetraenoate and 97% 15-hydroperoxyicosatetraenoate
L183E/L192E
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introduction of negatively charged residues at the intermonomer interface disturbs the hydrophobic dimer interaction of the wild-type LOX. Double mutant does not follow Michaelis-Menten kinetics. Double mutant are gradually inactivated at increasing substrate concentration
L367E
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L367F
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, in silico mutagenesis and structural modeling, L367 is involved in oxygen access, overview
L367K
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L367W
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
R403L
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a loss of electrostatic interaction between Arg403 and negatively charged amino acid residues of alpha2-helix has only minor impact on protein folding, but partially destabilizes the tertiary structure of the enzyme. Arg403Leu exchange induces strong substrate inhibition. kcat/Km values strongly decreased for linoleic acid and methyl arachidonate but almost unchanged for arachidonic acid compared to wild-type
W181E/H585E
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introduction of negatively charged residues at the intermonomer interface disturbs the hydrophobic dimer interaction of the wild-type LOX. Double mutant does not follow Michaelis-Menten kinetics. Double mutant are gradually inactivated at increasing substrate concentration
Y98A
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kcat and Km (linoleic acid) decreased compared to wild-type, mutant shows strongly reduced catalytic activity compared to wild-type
Y98R
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mutant shows strongly reduced catalytic activity compared to wild-type, mutant does not follow Michaelis-Menten-kinetics. Mutant is strongly inhibited by linoleic acid at concentrations above 0.01 mM
I419A
H2QBX9
naturally occuring mutation, the mutant produces exclusively 12-hydroperoxyicosatetraenoate and almost no 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces about 80% 15-hydroperoxyicosatetraenoate
I417A
naturally occuring mutation, the mutant produces 82% 12-hydroperoxyicosatetraenoate and 18% 15-hydroperoxyicosatetraenoate, in contrast to the wild-type, that produces 14% 12-hydroperoxyicosatetraenoate and 86% 15-hydroperoxyicosatetraenoate
M367V
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Km-value for arachidonic acid and turnover number are approximately double that of the wild-type enzyme
M562L
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Km-value for arachidonic acid is 77% of that of the wild type enzyme, turnover number is 85% of that of the wild type
V418I
V418I/419M
V418I/419M/353A
V418I/419M/353L
V419M
additional information
T560M
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naturally occurring enzyme mutant, the mutant shows 20fold reduced catalytic activity, genotyping using 12974 samples, the haplotypes show increased risk of coronary artery disease compared to non-carriers, overview
T560M
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mutant shows impaired catalytic activity, relative catalytic activity: 25% compared to wild-type 100%
W633X
naturally occurring mummy mutation, that introduces a nonsense codon into the C-terminal LOX catalytic domain, which results in truncation of the protein by 68 amino acids, mummy is identified in an ethylnitrosurea mutagenesis screen for autosomal recessive developmental phenotypes, the mutant is catalytically inactive, Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
W633X
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naturally occurring mummy mutation, that introduces a nonsense codon into the C-terminal LOX catalytic domain, which results in truncation of the protein by 68 amino acids, mummy is identified in an ethylnitrosurea mutagenesis screen for autosomal recessive developmental phenotypes, the mutant is catalytically inactive, Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
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V418I
mutant produces 21.5% of 12S- and 78.5% of 15S product
V418I
mutant produces 23.1% of 12S- and 76.9% of 15S product
V418I/419M
mutant produces 5.1% of 12S- and 94.9% of 15S product
V418I/419M
mutant produces 5.9% of 12S- and 94.1% of 15S product
V418I/419M/353A
mutant produces 89.6% of 12S- and 10.2% of 15S product
V418I/419M/353A
mutant produces 92.9% of 12S- and 7.1% of 15S product
V418I/419M/353L
mutant produces 16.9% of 12S- and 83.1% of 15S product
V418I/419M/353L
mutant produces 77.6% of 12S- and 22.4% of 15S product
V419M
mutant produces 5.46% of 12S- and 45.5% of 15S product
V419M
mutant produces 75.9% of 12S- and 24.1% of 15S product
additional information
construction of a soluble version of zf12-LOX by mutagenesis. Mutation of the putative calcium-responsive amino acids in N-PLAT domain of soluble zf12-LOX and analysis of the oligomeric state, stability, structural integrity and conformational changes of zf12-LOX in response to calcium. Soluble zf12-LOX and the N-PLAT domain-mutant both proteins exist as compact monomers in solution, and the enzyme activity of soluble zf12-LOX is significantly increased in presence of calcium, the stimulatory effect of calcium on zf12-LOX is related to a change in protein structure. In contrast, enzyme with a mutated calcium regulatory site has reduced activity-response to calcium and restricted large re-modeling, suggesting that it retains a closedstate in response to calcium. Ca2+-dependent regulation is associated with different domain conformation(s) that might change the accessibility to substrate-binding site in response to calcium
additional information
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construction of a soluble version of zf12-LOX by mutagenesis. Mutation of the putative calcium-responsive amino acids in N-PLAT domain of soluble zf12-LOX and analysis of the oligomeric state, stability, structural integrity and conformational changes of zf12-LOX in response to calcium. Soluble zf12-LOX and the N-PLAT domain-mutant both proteins exist as compact monomers in solution, and the enzyme activity of soluble zf12-LOX is significantly increased in presence of calcium, the stimulatory effect of calcium on zf12-LOX is related to a change in protein structure. In contrast, enzyme with a mutated calcium regulatory site has reduced activity-response to calcium and restricted large re-modeling, suggesting that it retains a closedstate in response to calcium. Ca2+-dependent regulation is associated with different domain conformation(s) that might change the accessibility to substrate-binding site in response to calcium
additional information
truncation of the N-terminal PLAT domain impairs catalytic activity but does not alter reaction specificity
additional information
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truncation of the N-terminal PLAT domain impairs catalytic activity but does not alter reaction specificity
additional information
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
additional information
generation of Alox15-deficient (12/15-LOX KO) mice
additional information
generation of enzyme-deficient Alox15-/- mice, phenotype, overview
additional information
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generation of enzyme-deficient Alox15-/- mice, phenotype, overview
additional information
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
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additional information
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generation of enzyme-deficient Alox15-/- mice, phenotype, overview
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additional information
the enzyme is involved in production of biologically active lipid mediators, (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate, 13-HODE, and 13-HOTE, in the intestine of iron-deficient Belgrade rats, the lipids are almoste absent in wild-type rats, overview
