Any feedback?
Information on EC 1.13.11.31 - arachidonate 12-lipoxygenase and Organism(s) Oryctolagus cuniculus and UniProt Accession P12530
for references in articles please use BRENDA:EC1.13.11.31Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.13.11.31 arachidonate 12-lipoxygenaseIUBMB Comments
The product is rapidly reduced to the corresponding 12S-hydroxy compound.
Specify your search results
Word Map
- 1.13.11.31
-
arachidonic
-
cyclooxygenase
-
12-hete
-
eicosanoids
- prostaglandin
- endothelial
- phospholipase
- neutrophil
- atherosclerosis
-
polyunsaturated
-
linoleic
- artery
- baicalein
-
lipoxins
-
hetes
- monocyte
-
12-hydroxyeicosatetraenoic
- cox-2
- reticulocyte
- asthma
-
nordihydroguaiaretic
-
thromboxane
-
eicosapentaenoic
- hydroperoxide
- ndga
-
polymorphonuclear
- atherogenesis
-
docosahexaenoic
- indomethacin
-
5,8,11,14-eicosatetraynoic
- etya
- zileuton
-
13-hode
-
hydroperoxy
- lipoxygenase-1
- erythroderma
-
hydroxyeicosatetraenoic
- medicine
- esculetin
-
protectins
-
ichthyosiform
-
resolvins
-
polyenoic
-
pro-resolving
- drug development
-
14carachidonic
- ichthyosis
-
ferroptosis
-
5-lipoxygenase-activating
- phenidone
-
a23187-stimulated
- oxylipins
The taxonomic range for the selected organisms is: Oryctolagus cuniculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
12-lipoxygenase, 15-lipoxygenase, 12-lox, alox5, 15-lox-1, alox15, 12-lo, 15-lo, 12/15-lipoxygenase, 12/15-lox, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
12-lipoxygenase
-
-
-
-
12-LOX
-
-
-
-
12/15-lipoxygenase
12DELTA-lipoxygenase
-
-
-
-
12S-lipoxygenase
-
-
-
-
C-12 lipoxygenase
-
-
-
-
DELTA 12-lipoxygenase
-
-
-
-
leukotriene A4 synthase M
-
-
-
-
LTA4 synthase
-
-
-
-
oygenase, arachidonate 12-lip-
-
-
-
-
Platelet-type lipoxygenase 12
-
-
-
-
12/15-lipoxygenase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
dioxygenation
-
-
-
-
dehydration
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
arachidonate:oxygen 12-oxidoreductase
The product is rapidly reduced to the corresponding 12S-hydroxy compound.
CAS REGISTRY NUMBER
COMMENTARY
82391-43-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
?
20-hydroxyeicosatetraenoic acid methyl ester + O2
8,20-dihydroxyeicosatetraenoic acid + 12,20-dihydroxyeicosatetraenoic acid + 9,20-dihydroxyeicosatetraenoic acid
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
linoleic acid methyl ester + O2
(9R)-hydroperoxy-(10E,12Z)-octadecadienoic acid methyl ester
-
-
-
-
?
methyl arachidonate + O2
(15S,5Z,8Z,11Z,13E)-15-hydroxy-5,8,11,13-eicosatetraenoic acid methyl ester
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
high oxygen affinity is important for effective catalysis, L367 is involved in oxygen access, channel structure, overview, arachidonic acid closes the substrate-binding pocket for oxygen diffusion but opens a fourth oxygen access channel
-
-
?
additional information
?
-
15-lipoxygenating ALOX15 orthologs exhibit significantly higher lipoxin-synthesizing capacities than 12-lipoxygenating. Product pattern of primate ALOX15 orthologues, overview. The wild-type animal produces 3% 12-hydroperoxyicosatetraenoate and 97% 15-hydroperoxyicosatetraenoate
-
-
?
additional information
?
-
-
15-lipoxygenating ALOX15 orthologs exhibit significantly higher lipoxin-synthesizing capacities than 12-lipoxygenating. Product pattern of primate ALOX15 orthologues, overview. The wild-type animal produces 3% 12-hydroperoxyicosatetraenoate and 97% 15-hydroperoxyicosatetraenoate
-
-
?
additional information
?
-
prediction of reaction specificity of mammalian ALOX15 orthologues, and reaction specificity of ALOX15 orthologues during late primate evolution
-
-
?
additional information
?
-
-
prediction of reaction specificity of mammalian ALOX15 orthologues, and reaction specificity of ALOX15 orthologues during late primate evolution
-
-
?
additional information
?
-
-
the bifunctional enzyme also forms (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate, the product of 15-LO activity, EC 1.13.11.33, in a ratio of 9:1 15(S)-HPETE to 12(S)-HPETE
-
-
?
additional information
?
-
-
binding of allosteric effector [13(S)-hydroxyoctadeca-9(Z),11(E)-dienoic acid] shifts the monomer-dimer equilibrium toward dimer formation
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
additional information
?
-
15-lipoxygenating ALOX15 orthologs exhibit significantly higher lipoxin-synthesizing capacities than 12-lipoxygenating. Product pattern of primate ALOX15 orthologues, overview. The wild-type animal produces 3% 12-hydroperoxyicosatetraenoate and 97% 15-hydroperoxyicosatetraenoate
-
-
?
additional information
?
-
-
15-lipoxygenating ALOX15 orthologs exhibit significantly higher lipoxin-synthesizing capacities than 12-lipoxygenating. Product pattern of primate ALOX15 orthologues, overview. The wild-type animal produces 3% 12-hydroperoxyicosatetraenoate and 97% 15-hydroperoxyicosatetraenoate
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
free-energy distribution for oxygen inside the substrate-free rabbit 12/15-LOX, containing four nested free-energy isosurfaces with different energy levels, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
mammals (mice, rats, pigs) express 12-lipoxygenating ALOX15 orthologues. 15-lipoxygenating isoforms are found in primates (orangutans, humans), suggesting an evolution of ALOX15 specificity. Other primates (baboons, rhesus monkeys) express 12-lipoxygenating enzymes. Gibbons, which are flanked in evolution by rhesus monkeys (12-lipoxygenating ALOX15) and orangutans (15-lipoxygenating ALOX15), express an ALOX15 ortholog with pronounced dual specificity, an evolution of ALOX15 specificity, which is aimed at optimizing the biosynthetic capacity for antiinflammatory and proresolving lipoxins. Phylogenetic analysis
physiological function
ALOX15-encoded 12/15-lipoxygenase orthologs are implicated in maturational degradation of intracellular organelles and in the biosynthesis of antiinflammatory and proresolving eicosanoids
additional information
additional information
molecular dynamics simulations and quantum mechanics/molecular mechanics calculations
additional information
-
molecular dynamics simulations and quantum mechanics/molecular mechanics calculations
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). LOX15_RABIT
663
0
75310
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
binding of allosteric effector [13(S)-hydroxyoctadeca-9(Z),11(E)-dienoic acid] shifts the monomer-dimer equilibrium toward dimer formation. Enzyme dimerization may protect the enzyme from kinetic substrate inhibition by shielding the hydrophobic alpha2 helixes
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
kcat and Km (linoleic acid) decreased compared to wild-type, mutant shows strongly reduced catalytic activity compared to wild-type
Y98R
-
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Meruvu Sunith, M.S.; Walther Matthia, W.M.; Ivanov Igo, I.I.; Hammarstrom Sve, H.S.; Furstenberger Gerhar, F.G.; Krieg Pete, K.P.; Reddanna Pall, R.P.; Kuhn Hartmu, K.H.
Sequence determinants for the reaction specificity of murine (12R)-lipoxygenase: targeted substrate modification and site-directed mutagenesis
J. Biol. Chem.
280
36633-36641
2005
Oryctolagus cuniculus
Saam, J.; Ivanov, I.; Walther, M.; Holzhuetter, H.G.; Kuhn, H.
Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels
Proc. Natl. Acad. Sci. USA
104
13319-13324
2007
Oryctolagus cuniculus
Ivanov, I.; Di Venere, A.; Horn, T.; Scheerer, P.; Nicolai, E.; Stehling, S.; Richter, C.; Skrzypczak-Jankun, E.; Mei, G.; Maccarrone, M.; Kuehn, H.
Tight association of N-terminal and catalytic subunits of rabbit 12/15-lipoxygenase is important for protein stability and catalytic activity
Biochim. Biophys. Acta
1811
1001-1010
2011
Oryctolagus cuniculus
Di Venere, A.; Horn, T.; Stehling, S.; Mei, G.; Masgrau, L.; Gonzalez-Lafont, A.; Kuehn, H.; Ivanov, I.
Role of Arg403 for thermostability and catalytic activity of rabbit 12/15-lipoxygenase
Biochim. Biophys. Acta
1831
1079-1088
2013
Oryctolagus cuniculus
Ivanov, I.; Shang, W.; Toledo, L.; Masgrau, L.; Svergun, D.; Stehling, S.; Gmez, H.; Di Venere, A.; Mei, G.; Lluch, J.; Skrzypczak-Jankun, E.; Gonzlez-Lafont, A.; Khn, H.
Ligand-induced formation of transient dimers of mammalian 12/15-lipoxygenase: A key to allosteric behavior of this class of enzymes?
Proteins
80
703-712
2012
Oryctolagus cuniculus
Adel, S.; Karst, F.; Gonzalez-Lafont, A.; Pekarova, M.; Saura, P.; Masgrau, L.; Lluch, J.M.; Stehling, S.; Horn, T.; Kuhn, H.; Heydeck, D.
Evolutionary alteration of ALOX15 specificity optimizes the biosynthesis of antiinflammatory and proresolving lipoxins
Proc. Natl. Acad. Sci. USA
113
E4266-E4275
2016
Pan paniscus, Homo sapiens neanderthalensis, Homo sapiens subsp. 'Denisova', Papio anubis (A0A096P2G1), Macaca mulatta (F7EPQ4), Macaca mulatta, Nomascus leucogenys (G1S6D2), Pan troglodytes (H2QBX9), Pan troglodytes, Oryctolagus cuniculus (P12530), Oryctolagus cuniculus, Homo sapiens (P16050), Pongo pygmaeus (Q5RBE8), Pongo pygmaeus, Pongo abelii (Q5RBE8)
EXTERNAL LINKS (specific for EC-Number 1.13.11.31)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
