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Literature summary for 3.3.2.6 extracted from

  • Mueller, M.J.; Blomster, M.; Oppermann, U.C.; Jornvall, H.; Samuelsson, B.; Haeggstrom, J.Z.
    Leukotriene A4 hydrolase: protection from mechanism-based inactivation by mutation of tyrosine-378 (1996), Proc. Natl. Acad. Sci. USA, 93, 5931-5935.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine the enzyme catalyses the hydrolysis of leukotriene A4 into the proinflammatory substance leukotriene B4 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
wild-type and mutant enzymes expressed in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
S379A 26% hydrolase activity, 4% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme Homo sapiens
S380A 54% hydrolase activity, 68% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme Homo sapiens
Y378F 173% hydrolase activity, 43% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme, mutant enzyme is resistant to suicide inactivation Homo sapiens
Y378Q 34% hydrolase activity, 1.6% peptidase activity, in comparison to 100% hydrolase- and peptidase activity of wild-type enzyme, mutant enzyme is resistant to suicide inactivation Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
leukotriene A4 suicide inactivation via an apparently mechanism-based irreversible binding of leukotriene A4 to the protein in a 1:1 stoichiometry, comparison of inactivation of wild-type and mutant enzymes, Tyr378 is a residue, which is involved in the binding of leukotriene A4 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.006
-
leukotriene A4 pH 8.0, 22°C, wild-type enzyme Homo sapiens
0.023
-
leukotriene A4 pH 8.0, 22°C, mutant Y378F Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Zinc zinc protein Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
leukotriene A4 + H2O Homo sapiens biosynthesis of leukotriene B4 leukotriene B4
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
0.692
-
in comparison with mutant enzymes Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
leukotriene A4 + H2O
-
Homo sapiens leukotriene B4
-
?
leukotriene A4 + H2O biosynthesis of leukotriene B4 Homo sapiens leukotriene B4
-
?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.85
-
leukotriene A4 pH 8.0, 22°C, wild-type enzyme Homo sapiens
2.09
-
leukotriene A4 pH 8.0, 22°C, mutant Y378F Homo sapiens