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Literature summary for 4.4.1.20 extracted from

  • Saino, H.; Ukita, Y.; Ago, H.; Irikura, D.; Nisawa, A.; Ueno, G.; Yamamoto, M.; Kanaoka, Y.; Lam, B.K.; Austen, K.F.; Miyano, M.
    The catalytic architecture of leukotriene C4 synthase with two arginine residues (2011), J. Biol. Chem., 286, 16392-16401.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Schizosaccharomyces pombe Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
wild-type to 1.9 A resolution, space group F23. Mutants R31A and R104A, space groups F23 and C222, respectively. The architecture for GSH binding is conserved. The GSH binding site is a V-shaped cleft at each intermonomer interface in the LTC4S trimer, and nine amino acid residues directly participate in the GSH binding. Residue R30 multiply binds the carboxyl group of the gamma-glutamyl moiety, and R104 interacts with both the thiol group and the carbonyl group of the cysteinyl moiety of GSH. The side chain of R31 is flexible in the crystal structure Homo sapiens

Protein Variants

Protein Variants Comment Organism
R104A substrate leukotriene A4, 2% of wild-type activity. No activity with substrate leukotriene A4 methyl ester Homo sapiens
R104Q substrate leukotriene A4, 2% of wild-type activity. No activity with substrate leukotriene A4 methyl ester Homo sapiens
R113A substrate leukotriene A4, 140% of wild-type activity Homo sapiens
R113Q substrate leukotriene A4, 150% of wild-type activity Homo sapiens
R31A substrate leukotriene A4, 6% of wild-type activity. No activity with substrate leukotriene A4 methyl ester Homo sapiens
R31E substrate leukotriene A4, 3% of wild-type activity Homo sapiens
R31L substrate leukotriene A4, 3% of wild-type activity Homo sapiens
R31Q substrate leukotriene A4, 32% of wild-type activity Homo sapiens
R90A substrate leukotriene A4, 6% of wild-type activity, substrate leukotriene A4 methyl ester, 21% ot wild-type activity Homo sapiens
R90Q substrate leukotriene A4, about 20% of wild-type activity Homo sapiens
R92A substrate leukotriene A4, about 95% of wild-type activity Homo sapiens
R92Q substrate leukotriene A4, about 105% of wild-type activity Homo sapiens
R99A substrate leukotriene A4, about 100% of wild-type activity Homo sapiens
R99Q substrate leukotriene A4, about 70% of wild-type activity Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00344
-
leukotriene A4 methyl ester wild-type, pH 8.0, 22°C Homo sapiens
0.00385
-
leukotriene A4 methyl ester mutant R104A, pH 7.0, 22°C Homo sapiens
0.00408
-
leukotriene A4 methyl ester wild-type, pH 7.0, 22°C Homo sapiens
0.00445
-
leukotriene A4 methyl ester wild-type, pH 9.0, 22°C Homo sapiens
0.00555
-
leukotriene A4 methyl ester mutant R31A, pH 8.0, 22°C Homo sapiens
0.00569
-
leukotriene A4 methyl ester mutant R104A, pH 9.0, 22°C Homo sapiens
0.00609
-
leukotriene A4 methyl ester mutant R31A, pH 7.0, 22°C Homo sapiens
0.00709
-
leukotriene A4 methyl ester mutant R104A, pH 8.0, 22°C Homo sapiens
0.00839
-
leukotriene A4 methyl ester mutant R31A, pH 9.0, 22°C Homo sapiens
0.054
-
glutathione mutant R31A, pH 8.0, 22°C Homo sapiens
0.067
-
glutathione mutant R31A, pH 9.0, 22°C Homo sapiens
0.104
-
glutathione mutant R31A, pH 7.0, 22°C Homo sapiens
0.188
-
glutathione wild-type, pH 8.0, 22°C Homo sapiens
0.189
-
glutathione wild-type, pH 9.0, 22°C Homo sapiens
0.52
-
glutathione wild-type, pH 7.0, 22°C Homo sapiens
12.8
-
glutathione mutant R104A, pH 8.0, 22°C Homo sapiens
16.7
-
glutathione mutant R104A, pH 7.0, 22°C Homo sapiens
24.6
-
glutathione mutant R104A, pH 9.0, 22°C Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q16873
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
leukotriene A4 + glutathione
-
Homo sapiens leukotriene C4
-
?
leukotriene A4 methyl ester + glutathione
-
Homo sapiens leukotriene C4 methyl ester
-
?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.019
-
leukotriene A4 methyl ester mutant R104A, pH 7.0, 22°C Homo sapiens
0.02
-
leukotriene A4 methyl ester mutant R31A, pH 8.0, 22°C Homo sapiens
0.021
-
leukotriene A4 methyl ester mutant R31A, pH 7.0, 22°C Homo sapiens
0.022
-
glutathione mutant R31A, pH 9.0, 22°C Homo sapiens
0.024
-
glutathione mutant R31A, pH 7.0, 22°C Homo sapiens
0.025
-
glutathione mutant R31A, pH 8.0, 22°C Homo sapiens
0.028
-
leukotriene A4 methyl ester mutant R31A, pH 9.0, 22°C Homo sapiens
0.053
-
leukotriene A4 methyl ester mutant R104A, pH 8.0, 22°C Homo sapiens
0.068
-
leukotriene A4 methyl ester mutant R104A, pH 9.0, 22°C Homo sapiens
0.069
-
glutathione mutant R104A, pH 7.0, 22°C Homo sapiens
0.196
-
glutathione mutant R104A, pH 8.0, 22°C Homo sapiens
0.233
-
glutathione mutant R104A, pH 9.0, 22°C Homo sapiens
1.69
-
leukotriene A4 methyl ester wild-type, pH 7.0, 22°C Homo sapiens
1.72
-
glutathione wild-type, pH 9.0, 22°C Homo sapiens
1.97
-
leukotriene A4 methyl ester wild-type, pH 8.0, 22°C Homo sapiens
2.1
-
leukotriene A4 methyl ester wild-type, pH 9.0, 22°C Homo sapiens
2.11
-
glutathione wild-type, pH 7.0, 22°C Homo sapiens
2.22
-
glutathione wild-type, pH 8.0, 22°C Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.46
-
glutathione mutant R31A, pH 8.0, 22°C Homo sapiens
0.93
-
glutathione mutant R104A, pH 8.0, 22°C Homo sapiens
2.8
-
glutathione wild-type, cosubstrate leukotriene A4, pH 7.0, 22°C Homo sapiens
3.63
-
leukotriene A4 methyl ester mutant R31A, pH 8.0, 22°C Homo sapiens
4.1
-
glutathione wild-type, cosubstrate leukotriene A4 methyl ester, pH 7.0, 22°C Homo sapiens
11.9
-
glutathione wild-type, pH 8.0, 22°C Homo sapiens
421
-
leukotriene A4 methyl ester wild-type, pH 7.0, 22°C Homo sapiens
577
-
leukotriene A4 methyl ester wild-type, pH 8.0, 22°C Homo sapiens
629
-
leukotriene A4 wild-type, pH 7.0, 22°C Homo sapiens