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Literature summary for 1.13.11.34 extracted from

  • Haefner, A.K.; Gerstmeier, J.; Hoernig, M.; George, S.; Ball, A.K.; Schroeder, M.; Garscha, U.; Werz, O.; Steinhilber, D.
    Characterization of the interaction of human 5-lipoxygenase with its activating protein FLAP (2015), Biochim. Biophys. Acta, 1851, 1465-1472 .
    View publication on PubMed

Activating Compound

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(Commentary)

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

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

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

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
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nucleoplasm accumulation of wild-type 5-LO in the soluble compartment of the nucleus, regardless of FLAP co-expression Homo sapiens 5654
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Metals/Ions

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens P09917
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
arachidonate + O2
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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

Synonyms Comment Organism
5-lipoxygenase
-
Homo sapiens
5-LO
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Homo sapiens

General Information

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