Activating Compound | Comment | Organism | Structure |
---|---|---|---|
FLAP | 5-lipoxygenase-activating protein, exclusively located at the nuclear membrane | Homo sapiens | |
phosphocholine | phosphocholine in combination with Ca2+ markedly stimulate the formation of leukotrienes by wild-type 5-LO and mutant C159S/C300S/C416S/C418S, whereas their effect on the 5-LO W13A/W75A/W102A mutant is small | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
gene ALOX5, recombinant expression of wild-type and mutant enzymes in HeLa cells, HEK-293 cells, and in Escherichia coli strain BL21 (DE3) | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
C159S/C300S/C416S/C418S | site-directed mutagenesis, the mutant shows unaltered product synthesis | Homo sapiens |
additional information | in vitro glutathionylation of recombinant purified 5-LO wild-type as well as 5-LO 4C, a mutant where the four surface cysteines are replaced by serines (Cys159/300/416/418Ser), does not alter product synthesis | Homo sapiens |
W13A/W75A/W102A | site-directed mutagenesis, the mutant is not activated by Ca2+ and phosphocholine | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
BWA4C | a direct inhibitor of 5-LO, treatment results not only in a suppression of leukotriene production, but in an almost complete inhibition of enzymatic | Homo sapiens | |
Diamide | in 5-LO/FLAP-transfected HeLa cells, treatment with the thiol-oxidizing agent diamide which promotes glutathionylation at surface Cys residues leads to a decreased leukotriene synthesis by wild-type 5-LO | Homo sapiens | |
additional information | treatement with FLAP inhibitor MK886 does not affect 5-H(p)ETE formation | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | being a mobile enzyme, 5-LO migrates from the cytosol to the nuclear envelope | Homo sapiens | 5829 | - |
additional information | immunohistochemic analysis of subcellular localization of recombinant wild-type and mutant enzymes in HeLa and HEK-293 cells | Homo sapiens | - |
- |
nuclear envelope | being a mobile enzyme, 5-LO migrates from the cytosol to the nuclear envelope, located mainly in the soluble part of the nucleus | Homo sapiens | 5635 | - |
nucleoplasm | accumulation of wild-type 5-LO in the soluble compartment of the nucleus, regardless of FLAP co-expression | Homo sapiens | 5654 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | phosphocholine in combination with Ca2+ markedly stimulate the formation of leukotrienes by wild-type 5-LO and C159S/C300S/C416S/C418S mutant, whereas their effect on the 5-LO 3W mutant is small | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | Homo sapiens | - |
(5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P09917 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | - |
Homo sapiens | (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? | |
additional information | detectable 5-LO products derived from conversion of arachidonate are quantified by HPLC and comprise 5-H(p)ETE (a mixture of 5-HETE (5S-hydroxy-6,8,11,14(E,Z,Z,Z)-eicosatetraenoic acid) and 5-HpETE (5S-hydroperoxy-6,8,11,14(E,Z,Z,Z)-eicosatetraenoic acid)) and the non-enzymatic hydrolysis products of leukotriene A4, 6-trans-leukotriene B4 (5S,12R-dihydroxy-6,8,10,14(E,E,E,Z)-eicosatetraenoic acid) and 6-trans-12-epi-LTB4 (5S,12S-dihydroxy-6,8,10,14-(E,E,E,Z)-eicosatetraenoic acid) | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
5-lipoxygenase | - |
Homo sapiens |
5-LO | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | in 5-LO/FLAP-transfected HeLa cells, treatment with the thiol-oxidizing agent diamide which promotes glutathionylation at surface Cys residues leads to a decreased leukotriene synthesis by wild-type 5-LO | Homo sapiens |
physiological function | being a mobile enzyme, 5-LO migrates from the cytosol to the nuclear envelope where it is believed to interact with 5-lipoxygenase-activating protein (FLAP) and receives the substrate arachidonic acid. Enzyme 5-LO is prone to redox regulation in the cell, e.g. 5-LO inhibition by glutathione peroxidase (GPX) 1 and 4 | Homo sapiens |