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Literature summary for 1.13.11.34 extracted from

  • Smyrniotis, C.J.; Barbour, S.R.; Xia, Z.; Hixon, M.S.; Holman, T.R.
    ATP allosterically activates the human 5-lipoxygenase molecular mechanism of arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid (2014), Biochemistry, 53, 4407-4419 .
    View publication on PubMedView publication on EuropePMC
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Activating Compound

Activating Compound Comment Organism Structure
ATP activates, hyperbolic kinetic parameters for ATP activation indicate a similar activation for arachidonate and (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate. Solvent isotope effect results for both hydroperoxidation and epoxidation indicate that a specific step in the molecular mechanism is changed, possibly because of a lowering of the dependence of the rate-limiting step on hydrogen atom abstraction and an increase in the dependency on hydrogen bond rearrangement. Changes in ATP concentration in the cell can affect the production of 5-LOX products, such as leukotrienes and lipoxins, and thus have wide implications for the regulation of cellular inflammation Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene 5-LOX, recombinant expression of the enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information steady-state kinetics and kinetic mechanism, overview. Kinetic parameters for ATP-induced activation of 5-LOX Homo sapiens
0.014
-
 (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate pH 7.5, 21°C, recombinant enzyme Homo sapiens
0.019
-
 arachidonate pH 7.5, 21°C, recombinant enzyme Homo sapiens
0.019
-
 (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate pH 7.5, 21°C, recombinant enzyme, with 0.2 mM ATP Homo sapiens
0.053
-
 arachidonate pH 7.5, 21°C, recombinant enzyme, with 0.2 mM ATP Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane calcium binds to allosteric sites in the 5-LOX N-terminal polycystin-1/lipoxygenase/alpha-toxin (PLAT) domain, promoting attachment to the membrane via conserved tryptophan residues that embed into the lipid bilayer Homo sapiens 16020
-

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ 5-LOX is recruited to the nuclear membrane upon cellular Ca2+ influx. Calcium binds to allosteric sites in the 5-LOX N-terminal polycystin-1/lipoxygenase/alpha-toxin (PLAT) domain, promoting attachment to the membrane via conserved tryptophan residues that embed into the lipid bilayer Homo sapiens
Fe2+ requied for activity Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate Homo sapiens epoxidation (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
-
 ?
arachidonate + O2 Homo sapiens
-
 (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P09917
-
-

Reaction

Reaction Comment Organism Reaction ID
arachidonate + O2 = (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoate kinetic mechainsm, overview Homo sapiens
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate epoxidation Homo sapiens (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O
-
 ?
arachidonate + O2
-
 Homo sapiens (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate
-
 ?
arachidonate + O2 hydroperoxidation Homo sapiens (5S,6E,8Z,11Z,14Z)-5-hydroperoxyicosa-6,8,11,14-tetraenoate
-
 ?

Synonyms

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

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
21
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function changes in 5-LOX activator ATP concentration in the cell can affect the production of 5-LOX products, such as leukotrienes and lipoxins, and thus have wide implications for the regulation of cellular inflammation. The enzyme is involved in the synthesis of leukotrienes B4 and A4, important metabolites of the regulation of inflammation. 5-LOX catalytic activity is regulated through several mechanisms by the cell. 5-LOX is recruited to the nuclear membrane upon cellular Ca2+ influx. Calcium binds to allosteric sites in the 5-LOX N-terminal polycystin-1/lipoxygenase/alpha-toxin (PLAT) domain, promoting attachment to the membrane via conserved tryptophan residues that embed into the lipid bilayer Homo sapiens