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Literature summary extracted from

  • Niegowski, D.; Kleinschmidt, T.; Olsson, U.; Ahmad, S.; Rinaldo-Matthis, A.; Haeggstroem, J.Z.
    Crystal structures of leukotriene C4 synthase in complex with product analogs: implications for the enzyme mechanism (2014), J. Biol. Chem., 289, 5199-5207.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
4.4.1.20 recombinant expression of wild-type and mutant enzymes in Pichia pastoris strain KM71H Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
4.4.1.20 purified enzyme in apoform or in complex with either one of three product analogues, S-hexyl-, 4-phenyl-butyl-, and 2-hydroxy-4-phenyl-butyl-glutathione, sitting drop vapor diffusion, mixing of 0.001 ml of 3.5 mg/ml protein solution containing 1 mM GSH with 0.001 ml of reservoir solution containing 1.8-2.2 M NH4SO4, 0.2 M NaCl, and 0.1 M sodium cacodylate, pH 6.1-6.8, 1-4 days, room temperature, soaking in 1 mM ligand solutions, X-ray diffraction structure determination and analysis at 2.4-3.2 A resolution Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
4.4.1.20 W116A site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
4.4.1.20 W116F site-directed mutagenesis, the mutant shows a 3fold increased turnover of leukotriene A4 compared to the wild-type enzyme Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
4.4.1.20 0.03
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
4.4.1.20 0.04
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant mutant W116A Homo sapiens
4.4.1.20 0.095
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant mutant W116F Homo sapiens
4.4.1.20 0.3
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
4.4.1.20 1.42
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant mutant W116A Homo sapiens
4.4.1.20 2.38
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant mutant W116F Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
4.4.1.20 endoplasmic reticulum membrane integral membrane protein in the outer leaflet of the nuclear envelope and in the endoplasmic reticulum Homo sapiens 5789
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.4.1.20 leukotriene A4 + glutathione Homo sapiens
-
 leukotriene C4
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
4.4.1.20 Homo sapiens Q16873
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.4.1.20 leukotriene A4 + glutathione
-
 Homo sapiens leukotriene C4
-
 ?
4.4.1.20 leukotriene A4 + glutathione glutathione-enzyme binding structure, overview Homo sapiens leukotriene C4 i.e. (5S)-hydroxy-(6R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic acid ?

Synonyms

EC Number Synonyms Comment Organism
4.4.1.20 leukotriene C4 synthase
-
 Homo sapiens
4.4.1.20 LT C4 synthase
-
 Homo sapiens
4.4.1.20 LTC4S
-
 Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
4.4.1.20 12
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
4.4.1.20 16.8
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant mutant W116A Homo sapiens
4.4.1.20 17.7
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant mutant W116F Homo sapiens
4.4.1.20 26
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
4.4.1.20 32
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant mutant W116A Homo sapiens
4.4.1.20 74.3
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant mutant W116F Homo sapiens

General Information

EC Number General Information Comment Organism
4.4.1.20 evolution the enzyme belongs to the superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism, which consists of six integral membrane proteins Homo sapiens
4.4.1.20 additional information enzyme residue Trp116 is not essential for catalysis but helps position the omega-end of leukotriene A4 Homo sapiens
4.4.1.20 physiological function the enzyme catalyzes the conjugation reaction between the fatty acid leukotriene A4 and GSH to form the pro-inflammatory leukotriene C4, an important mediator of asthma Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
4.4.1.20 7
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant mutant W116F Homo sapiens
4.4.1.20 11
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant mutant W116A Homo sapiens
4.4.1.20 40
-
 leukotriene A4 pH 7.8, temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
4.4.1.20 730
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant mutant W116F Homo sapiens
4.4.1.20 810
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant mutant W116A Homo sapiens
4.4.1.20 870
-
 glutathione pH 7.8, temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens