Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | ALOX15 is usually present as catalytically silent ferrous enzyme. To initiate fatty acid oxygenation, the enzyme must first be oxidized to a ferric form capable of initiating hydrogen abstraction. Unfortunately, single activation of the enzyme is not sufficient to keep it running, since during catalysis small quantities of radical intermediates might escape from the active site leaving the enzyme in an inactive ferrous (Fe2+) form. To keep the reaction at quasistationary levels, repeated enzyme activation is required and the primary oxygenation products appear to serve as enzyme activators. In this sense, the LOX exhibits autocatalytic properties | Rattus norvegicus | |
additional information | ALOX15 is usually present as catalytically silent ferrous enzyme. To initiate fatty acid oxygenation, the enzyme must first be oxidized to a ferric form capable of initiating hydrogen abstraction. Unfortunately, single activation of the enzyme is not sufficient to keep it running, since during catalysis small quantities of radical intermediates might escape from the active site leaving the enzyme in an inactive ferrous (Fe2+) form. To keep the reaction at quasistationary levels, repeated enzyme activation is required and the primary oxygenation products appear to serve as enzyme activators. In this sense, the LOX exhibits autocatalytic properties | Homo sapiens | |
additional information | ALOX15 is usually present as catalytically silent ferrous enzyme. To initiate fatty acid oxygenation, the enzyme must first be oxidized to a ferric form capable of initiating hydrogen abstraction. Unfortunately, single activation of the enzyme is not sufficient to keep it running, since during catalysis small quantities of radical intermediates might escape from the active site leaving the enzyme in an inactive ferrous (Fe2+) form. To keep the reaction at quasistationary levels, repeated enzyme activation is required and the primary oxygenation products appear to serve as enzyme activators. In this sense, the LOX exhibits autocatalytic properties | Mus musculus | |
additional information | ALOX15 is usually present as catalytically silent ferrous enzyme. To initiate fatty acid oxygenation, the enzyme must first be oxidized to a ferric form capable of initiating hydrogen abstraction. Unfortunately, single activation of the enzyme is not sufficient to keep it running, since during catalysis small quantities of radical intermediates might escape from the active site leaving the enzyme in an inactive ferrous (Fe2+) form. To keep the reaction at quasistationary levels, repeated enzyme activation is required and the primary oxygenation products appear to serve as enzyme activators. In this sense, the LOX exhibits autocatalytic properties. Studying the oxygenation of 15S-HETE by pure rabbit ALOX15, it is found that the corresponding oxygenation product(s) does not activate the enzyme, while molecular dioxygen serves not only as a lipoxygenase substrate, but also impacts peroxide-dependent enzyme activation | Oryctolagus cuniculus |
Crystallization (Comment) | Organism |
---|---|
X-ray diffraction crystal structure determination and analysis at 2.4 A resolution | Oryctolagus cuniculus |
Protein Variants | Comment | Organism |
---|---|---|
Q548L | site-directed mutagenesis, the mutation disrupts the hydrogen bond network inducing a loss in catalytic activity suggesting that this mutation might alter the structure of the iron cluster | Oryctolagus cuniculus |
General Stability | Organism |
---|---|
purified rabbit ALOX15 is surprisingly stable when digested with proteases in vitro. Even long-term incubations (up to two hours) of purified rabbit ALOX15 with 0.5% trypsin does only lead to minor impairment of the catalytic activity with absolute conservation of the product specificity | Oryctolagus cuniculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
AA-861 | - |
Homo sapiens | |
AA-861 | - |
Mus musculus | |
AA-861 | - |
Oryctolagus cuniculus | |
AA-861 | - |
Rattus norvegicus | |
baicalein | - |
Homo sapiens | |
baicalein | - |
Mus musculus | |
baicalein | - |
Oryctolagus cuniculus | |
baicalein | - |
Rattus norvegicus | |
CDC | CAS-No. 132465-11-3 | Homo sapiens | |
CDC | CAS-No. 132465-11-3 | Mus musculus | |
CDC | CAS-No. 132465-11-3 | Oryctolagus cuniculus | |
CDC | CAS-No. 132465-11-3 | Rattus norvegicus | |
gallic acid | - |
Homo sapiens | |
gallic acid | - |
Mus musculus | |
gallic acid | - |
Oryctolagus cuniculus | |
gallic acid | - |
Rattus norvegicus | |
additional information | certain oxazole-4-carbonitrile based LOX inhibitors share a high inhibitory potency for human and mouse ALOX15 but hardly inhibit other mammalian LOX-isoforms | Homo sapiens | |
additional information | certain oxazole-4-carbonitrile based LOX inhibitors share a high inhibitory potency for human and mouse ALOX15 but hardly inhibit other mammalian LOX-isoforms | Mus musculus | |
additional information | certain oxazole-4-carbonitrile based LOX inhibitors share a high inhibitory potency for human and mouse ALOX15 but hardly inhibit other mammalian LOX-isoforms | Oryctolagus cuniculus | |
additional information | certain oxazole-4-carbonitrile based LOX inhibitors share a high inhibitory potency for human and mouse ALOX15 but hardly inhibit other mammalian LOX-isoforms | Rattus norvegicus | |
nordihydroguaiaretic acid | - |
Homo sapiens | |
nordihydroguaiaretic acid | - |
Mus musculus | |
nordihydroguaiaretic acid | - |
Oryctolagus cuniculus | |
nordihydroguaiaretic acid | - |
Rattus norvegicus | |
PD146176 | - |
Homo sapiens | |
PD146176 | - |
Mus musculus | |
PD146176 | - |
Oryctolagus cuniculus | |
PD146176 | - |
Rattus norvegicus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | enzyme-bound, required for catalysis | Rattus norvegicus | |
Fe2+ | enzyme-bound, required for catalysis | Homo sapiens | |
Fe2+ | enzyme-bound, required for catalysis | Mus musculus | |
Fe2+ | enzyme-bound, required for catalysis | Oryctolagus cuniculus |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
75000 | - |
- |
Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | Rattus norvegicus | - |
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
arachidonate + O2 | Homo sapiens | - |
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
arachidonate + O2 | Mus musculus | - |
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
arachidonate + O2 | Oryctolagus cuniculus | - |
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
additional information | Rattus norvegicus | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation | ? | - |
? | |
additional information | Mus musculus | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation | ? | - |
? | |
additional information | Oryctolagus cuniculus | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation | ? | - |
? | |
additional information | Homo sapiens | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation. Intraenzyme oxygen movement | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P16050 | - |
- |
Mus musculus | P39654 | - |
- |
Oryctolagus cuniculus | P12530 | - |
- |
Rattus norvegicus | Q02759 | - |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | the reaction proceeds via hydrogen abstraction, peroxide cleavage, radical rearrangement, and epoxide formation. To initiate the reaction the ferrous LOX is first activated by peroxide-dependent oxidation to a ferric form. The lipohydroperoxidase activity is initiatedwhen a lipid hydroperoxide (ROOH) is bound at the active site of the enzyme. The enzyme then catalyzes a homolytic cleavage of the hydroperoxy bond, which leads to the formation of an oxygen-centered alkoxy radical, a hydroxyl and oxidizes the ferrous iron to a ferric form. Then the enzyme binds a linoleic acid molecule (or an alterative reductant such as guaiacol) and releases a carbon-centered linoleic radical. This reaction reduces the ferric LOX back to its ferrous form to start the next catalytic cycle. The released radical intermediates may then initiate free radical secondary reactions leading to the formation of mixed oxygenated and non-oxygenated linoleic acid dimer | Rattus norvegicus | |
arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | the reaction proceeds via hydrogen abstraction, peroxide cleavage, radical rearrangement, and epoxide formation. To initiate the reaction the ferrous LOX is first activated by peroxide-dependent oxidation to a ferric form. The lipohydroperoxidase activity is initiatedwhen a lipid hydroperoxide (ROOH) is bound at the active site of the enzyme. The enzyme then catalyzes a homolytic cleavage of the hydroperoxy bond, which leads to the formation of an oxygen-centered alkoxy radical, a hydroxyl and oxidizes the ferrous iron to a ferric form. Then the enzyme binds a linoleic acid molecule (or an alterative reductant such as guaiacol) and releases a carbon-centered linoleic radical. This reaction reduces the ferric LOX back to its ferrous form to start the next catalytic cycle. The released radical intermediates may then initiate free radical secondary reactions leading to the formation of mixed oxygenated and non-oxygenated linoleic acid dimer | Homo sapiens | |
arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | the reaction proceeds via hydrogen abstraction, peroxide cleavage, radical rearrangement, and epoxide formation. To initiate the reaction the ferrous LOX is first activated by peroxide-dependent oxidation to a ferric form. The lipohydroperoxidase activity is initiatedwhen a lipid hydroperoxide (ROOH) is bound at the active site of the enzyme. The enzyme then catalyzes a homolytic cleavage of the hydroperoxy bond, which leads to the formation of an oxygen-centered alkoxy radical, a hydroxyl and oxidizes the ferrous iron to a ferric form. Then the enzyme binds a linoleic acid molecule (or an alterative reductant such as guaiacol) and releases a carbon-centered linoleic radical. This reaction reduces the ferric LOX back to its ferrous form to start the next catalytic cycle. The released radical intermediates may then initiate free radical secondary reactions leading to the formation of mixed oxygenated and non-oxygenated linoleic acid dimer | Mus musculus | |
arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | the reaction proceeds via hydrogen abstraction, peroxide cleavage, radical rearrangement, and epoxide formation. To initiate the reaction the ferrous LOX is first activated by peroxide-dependent oxidation to a ferric form. The lipohydroperoxidase activity is initiatedwhen a lipid hydroperoxide (ROOH) is bound at the active site of the enzyme. The enzyme then catalyzes a homolytic cleavage of the hydroperoxy bond, which leads to the formation of an oxygen-centered alkoxy radical, a hydroxyl and oxidizes the ferrous iron to a ferric form. Then the enzyme binds a linoleic acid molecule (or an alterative reductant such as guaiacol) and releases a carbon-centered linoleic radical. This reaction reduces the ferric LOX back to its ferrous form to start the next catalytic cycle. The released radical intermediates may then initiate free radical secondary reactions leading to the formation of mixed oxygenated and non-oxygenated linoleic acid dimer | Oryctolagus cuniculus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
airway epithelial cell | - |
Homo sapiens | - |
brain | - |
Homo sapiens | - |
eosinophil | - |
Homo sapiens | - |
erythrocyte | immature | Homo sapiens | - |
leukocyte | - |
Homo sapiens | - |
macrophage | alveolar | Homo sapiens | - |
macrophage | high level expression in peritoneal macrophages, while murine peripheral monocytes, alveolar macrophages and bone marrow-derived macrophages express alox15 only at low levels | Mus musculus | - |
additional information | tissue specific expression of ALOX15 and transcriptional expression regulation, overview | Rattus norvegicus | - |
additional information | tissue specific expression of ALOX15 and transcriptional expression regulation, overview | Mus musculus | - |
additional information | tissue specific expression of ALOX15 and transcriptional expression regulation, overview | Oryctolagus cuniculus | - |
additional information | tissue specific expression of ALOX15 and transcriptional expression regulation, overview. In humans ALOX15 is constitutively expressed at high levels in immature red blood cells, in eosinophils and in airway epithelial cells. Human peripheral blood monocytes do not express ALOX15 | Homo sapiens | - |
uterus | - |
Homo sapiens | - |
vascular cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
1-palmitoyl-2-arachidonyl phosphatidyl choline + O2 | - |
Oryctolagus cuniculus | 15S-HpETE + ? | - |
? | |
1-palmitoyl-2-docosahexaenoyl phosphatidyl choline + O2 | - |
Oryctolagus cuniculus | 17S-HpDHE + ? | - |
? | |
1-palmitoyl-2-eicosapentaenoyl phosphatidyl choline + O2 | - |
Oryctolagus cuniculus | 15S-HpEPE + ? | - |
? | |
1-palmitoyl-2-linoleoyl phosphatidyl choline + O2 | - |
Oryctolagus cuniculus | 13S-HpODE + ? | - |
? | |
1-stearoyl-2-arachidonoyl glycerol + O2 | - |
Oryctolagus cuniculus | 15-HETE + ? | - |
? | |
1-stearoyl-2-linoleoyl glycerol + O2 | - |
Oryctolagus cuniculus | 13S-HPODE + ? | - |
? | |
arachidonate + O2 | - |
Rattus norvegicus | (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
arachidonate + O2 | - |
Homo sapiens | (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
arachidonate + O2 | - |
Mus musculus | (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
arachidonate + O2 | - |
Oryctolagus cuniculus | (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate | - |
? | |
cholesteryl arachidonate + O2 | - |
Oryctolagus cuniculus | 15S-HpETE + ? | - |
? | |
cholesteryl linoleate + O2 | - |
Oryctolagus cuniculus | 13S-HpODE + ? | - |
? | |
cholesteryl linolenate + O2 | - |
Oryctolagus cuniculus | 13S-HpOTE + ? | - |
? | |
additional information | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation | Rattus norvegicus | ? | - |
? | |
additional information | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation | Mus musculus | ? | - |
? | |
additional information | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation | Oryctolagus cuniculus | ? | - |
? | |
additional information | the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation. Intraenzyme oxygen movement | Homo sapiens | ? | - |
? | |
additional information | enzyme substrate specificity, overview. The ALOX15 enzyme activity is not restricted to free polyenoic fatty acids since phospholipids and even biomembranes and lipoproteins are suitable ALOX15 substrates. The ALOX15 orthologue is capable of converting hydroperoxy fatty acids to epoxy leukotrienes. Molecular docking studies of a phospholipid molecule at the active site of rabbit ALOX15. Product specificity with polyenoic acids and with complex substrates, and alteration of product specificity by substrate modification. Intraenzyme oxygen movement | Oryctolagus cuniculus | ? | - |
? | |
additional information | enzyme substrate specificity, overview. The ALOX15 enzyme activity is not restricted to free polyenoic fatty acids since phospholipids and even biomembranes and lipoproteins are suitable ALOX15 substrates. The ALOX15 orthologue is capable of converting hydroperoxy fatty acids to epoxy leukotrienes. Product specificity with polyenoic acids and with complex substrates, and alteration of product specificity by substrate modification | Homo sapiens | ? | - |
? | |
additional information | enzyme substrate specificity, overview. The ALOX15 enzyme activity is not restricted to free polyenoic fatty acids since phospholipids and even biomembranes and lipoproteins are suitable ALOX15 substrates. The ALOX15 orthologue is capable of converting hydroperoxy fatty acids to epoxy leukotrienes. Product specificity with polyenoic acids and with complex substrates, and alteration of product specificity by substrate modification. Intraenzyme oxygen movement | Rattus norvegicus | ? | - |
? | |
additional information | enzyme substrate specificity, overview. The ALOX15 enzyme activity is not restricted to free polyenoic fatty acids since phospholipids and even biomembranes and lipoproteins are suitable ALOX15 substrates. The ALOX15 orthologue is capable of converting hydroperoxy fatty acids to epoxy leukotrienes. Product specificity with polyenoic acids and with complex substrates, and alteration of product specificity by substrate modification. Intraenzyme oxygen movement | Mus musculus | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 75000 | Homo sapiens |
More | mammalian ALOX15 enzyme structure comparisons, overview | Rattus norvegicus |
More | mammalian ALOX15 enzyme structure comparisons, overview | Mus musculus |
More | mammalian ALOX15 enzyme structure comparisons, overview. The enzyme contains 11 cysteine residues but no disulfide bridge | Homo sapiens |
More | mammalian ALOX15 enzyme structure comparisons, overview. The single polypeptide chain of rabbit ALOX15 folds into a two-domain structure: a small N-terminal beta-barrel domain and a larger mostly helical catalytic domain. The small N-terminal domain comprises 110 amino acids and is composed of 8 beta-sheets. The C-terminal catalytic domain of ALOX15 (residues 114-663) consists of 21 helices, which are interrupted by a small beta-sheet subdomain. In the crystal structure of the rabbit ALOX15-inhibitor complex (PDB ID 2P0M) the enzyme is present as protein dimer, in which the hydrophobic Leu179, Leu183, Leu188, and Leu192 form a cluster, which resembles a leucine-zipper like motif | Oryctolagus cuniculus |
Synonyms | Comment | Organism |
---|---|---|
Alox15 | - |
Rattus norvegicus |
Alox15 | - |
Homo sapiens |
Alox15 | - |
Mus musculus |
Alox15 | - |
Oryctolagus cuniculus |
arachidonic acid 15-lipoxygenase-1 | - |
Rattus norvegicus |
arachidonic acid 15-lipoxygenase-1 | - |
Homo sapiens |
arachidonic acid 15-lipoxygenase-1 | - |
Mus musculus |
arachidonic acid 15-lipoxygenase-1 | - |
Oryctolagus cuniculus |
Organism | Comment | pI Value Maximum | pI Value |
---|---|---|---|
Oryctolagus cuniculus | - |
- |
5.5 |
General Information | Comment | Organism |
---|---|---|
evolution | LOX isozymes and classification systems, overview | Rattus norvegicus |
evolution | LOX isozymes and classification systems, overview | Homo sapiens |
evolution | LOX isozymes and classification systems, overview | Mus musculus |
evolution | LOX isozymes and classification systems, overview | Oryctolagus cuniculus |
physiological function | lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which are implicated in a number of physiological processes and in the pathogenesis of inflammatory, hyperproliferative and neurodegenerative diseases. Physiological roles of ALOX15, detailed overview | Rattus norvegicus |
physiological function | lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which are implicated in a number of physiological processes and in the pathogenesis of inflammatory, hyperproliferative and neurodegenerative diseases. Physiological roles of ALOX15, detailed overview | Homo sapiens |
physiological function | lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which are implicated in a number of physiological processes and in the pathogenesis of inflammatory, hyperproliferative and neurodegenerative diseases. Physiological roles of ALOX15, detailed overview | Mus musculus |
physiological function | lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which are implicated in a number of physiological processes and in the pathogenesis of inflammatory, hyperproliferative and neurodegenerative diseases. Physiological roles of ALOX15, detailed overview | Oryctolagus cuniculus |