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Information on EC 4.4.1.20 - leukotriene-C4 synthase and Organism(s) Mus musculus and UniProt Accession Q60860

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EC Tree
IUBMB Comments
The reaction proceeds in the direction of addition. Not identical with EC 2.5.1.18, glutathione transferase.
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This record set is specific for:
Mus musculus
UNIPROT: Q60860
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Synonyms
ltc4s, ltc4 synthase, leukotriene c4 synthase, ltc4 synthetase, leukotriene-c4 synthase, leukotriene c4 synthetase, lt c4 synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
leukotriene C4 synthase
-
leukotriene C4 synthetase
-
LT C4 synthase
-
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate:glutathione leukotriene-transferase (epoxide-ring-opening)
-
-
-
-
leukotriene A4:glutathione S-leukotrienyltransferase
-
-
-
-
leukotriene C4 synthase
-
-
-
-
leukotriene C4 synthetase
-
-
-
-
LTC4 synthase
-
-
-
-
LTC4 synthetase
-
-
-
-
synthase, leukotriene C4
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alkenyl group transfer
alkenyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
leukotriene-C4 glutathione-lyase (leukotriene-A4-forming)
The reaction proceeds in the direction of addition. Not identical with EC 2.5.1.18, glutathione transferase.
CAS REGISTRY NUMBER
COMMENTARY hide
90698-32-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
leukotriene A4 + glutathione
leukotriene C4
show the reaction diagram
leukotriene A4 + glutathione
leukotriene C4 + H2O
show the reaction diagram
leukotriene A4 methyl ester + glutathione
leukotriene C4 methyl ester + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
leukotriene A4 + glutathione
leukotriene C4
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
enhances activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-benzoyl-5-(5-[(4-chlorophenyl)(methyl)amino]pyridine-2-carbonyl)benzoic acid
i.e. TK04, competitive mode of binding versus leukotriene A4
Tumor necrosis factor alpha
-
-
indomethacin
MK-886
Rose bengal
-
IC50: 0.05 mM
Triphenyltin chloride
-
poor inhibitor
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.2
glutathione
pH 7.8, temperature not specified in the publication, recombinant enzyme
0.036
leukotriene A4
pH 7.8, temperature not specified in the publication, recombinant enzyme
0.36
glutathione
-
pH 7.5, 37Ā°C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
84
glutathione
pH 7.8, temperature not specified in the publication, recombinant enzyme
81
leukotriene A4
pH 7.8, temperature not specified in the publication, recombinant enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
68
glutathione
pH 7.8, temperature not specified in the publication, recombinant enzyme
2300
leukotriene A4
pH 7.8, temperature not specified in the publication, recombinant enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000037
2-benzoyl-5-(5-[(4-chlorophenyl)(methyl)amino]pyridine-2-carbonyl)benzoic acid
pH 7.8, temperature not specified in the publication, recombinant enzyme
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000135
2-benzoyl-5-(5-[(4-chlorophenyl)(methyl)amino]pyridine-2-carbonyl)benzoic acid
Mus musculus
pH 7.8, temperature not specified in the publication, recombinant enzyme
1
indomethacin
Mus musculus
-
IC50: 1.0 mM
0.0031
MK-886
Mus musculus
-
IC50: 0.0031 mM
0.05
Rose bengal
Mus musculus
-
IC50: 0.05 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30.5
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
emanating from the vasopressinergic magnocellular neurons of the hypothalamic paraventricular, supraoptic and suprachiasmatic nuclei as well as the retrochiasmatic area to the pars nervosa of the pituitary gland. It is also observed in the axons of the extrahypothalamic system
Manually annotated by BRENDA team
integral membrane protein in the outer leaflet of the nuclear envelope and in the endoplasmic reticulum
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme belongs to the superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism, which consists of six integral membrane proteins. Although structural differences near the active site and along the C-terminal alpha-helix V suggest that the mouse and human enzymes may function differently in vivo
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
LTC4S_MOUSE
150
3
16814
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18000
3 * 18000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
trimer
3 * 18000
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in apoform or in complex with substrate glutathione or product analogue S-hexyl-GSH, mixing of 0.001 ml of 3.5 mg/ml protein in 0.03% w/v DDM w/v, 20 mM Tris pH 8.0, 100 mM NaCl, and 0.5 mM TCEP, with or without 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 Na cacodylate pH 6.1-6.8, for S-hexyl GSH-enzyme crystals, S-hexyl GSH is added to mother liquor and soaking of apo-crystals, X-ray diffraction structure determination and analysis at 2.65-2.7 A resolution
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partial
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli, construction of an enhanced green fluorescent protein under the control of the mouse leukotriene C4 synthase promoter
recombinant enzyme expression in Pichia pastoris strain KM71H
COS-7 cells transfected with either human or cloned mouse leukotriene C4 synthase cDNA by DEAE-dextran transfection
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
although structural differences near the active site and along the C-terminal alpha-helix V suggest that the mouse and human enzymes may function differently in vivo, the mouse enzyme is a useful tool in pharmacological research and drug development
drug development
although structural differences near the active site and along the C-terminal alpha-helix V suggest that the mouse and human enzymes may function differently in vivo, the mouse enzyme is a useful tool in pharmacological research and drug development
molecular biology
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Penrose, J.F.; Austen, K.F.
The biochemical, molecular, and genomic aspects of leukotriene C4 synthase
Proc. Assoc. Am. Phys.
111
537-546
1999
Cavia porcellus, Homo sapiens, Mus musculus
-
Manually annotated by BRENDA team
Hevko, J.M.; Murphy, R.C.
Formation of murine macrophage-derived 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid (FOG7) is catalyzed by leukotriene C4 synthase
J. Biol. Chem.
277
7037-7043
2002
Mus musculus
Manually annotated by BRENDA team
Söderström, M.; Hammarström, S.; Mannervik, B.
Leukotriene C synthase in mouse mastocytoma cells. An enzyme distinct from cytosolic and microsomal glutathione transferases
Biochem. J.
250
713-718
1988
Mus musculus
Manually annotated by BRENDA team
Abe, M.; Hugli, T.E.
Characterization of leukotriene C4 synthetase in mouse peritoneal exudate cells
Biochim. Biophys. Acta
959
386-398
1988
Mus musculus
Manually annotated by BRENDA team
Soederstroem, M.; Morgenstern, R.; Hammarstroem, S.
Protein-protein interaction affinity chromatography of leukotriene C4 synthase
Protein Expr. Purif.
6
352-356
1995
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Goppelt-Struebe, M.
Two step purification of human and murine leukotriene C4 synthase
Biochim. Biophys. Acta
1256
257-261
1995
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Lam, B.K.; Frank Austen, K.
Leukotriene C4 synthase: a pivotal enzyme in cellular biosynthesis of the cysteinyl leukotrienes
Prostaglandins Other Lipid Mediat.
68-69
511-520
2002
Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Söderström, M.; Mannervik, B.; Mammarström, S.
Leukotriene C4 synthase: characterization in mouse mastocytoma cells
Methods Enzymol.
187
306-312
1990
Mus musculus
Manually annotated by BRENDA team
Lam, B.K.; Penrose, J.F.; Rokach, J.; Xu, K.; Baldasaro, M.H.; Austen, K.F.
Molecular cloning, expression and characterization of mouse leukotriene C4 synthase
Eur. J. Biochem.
238
606-612
1996
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Shimada, A.; Satoh, M.; Chiba, Y.; Saitoh, Y.; Kawamura, N.; Keino, H.; Hosokawa, M.; Shimizu, T.
Highly selective localization of leukotriene C4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain
Neuroscience
131
683-689
2005
Mus musculus (Q60860), Mus musculus
Manually annotated by BRENDA team
Serio, K.J.; Luo, C.; Luo, L.; Mao, J.T.
TNF-alpha downregulates the leukotriene C4 synthase gene in mononuclear phagocytes
Am. J. Physiol. Lung Cell Mol. Physiol.
292
L215-L222
2007
Mus musculus (Q60860), Mus musculus
Manually annotated by BRENDA team
Strid, T.; Soederstroem, M.; Hammarstroem, S.
Leukotriene C4 synthase promoter driven expression of GFP reveals cell specificity
Biochem. Biophys. Res. Commun.
366
80-85
2008
Mus musculus (Q60860), Mus musculus
Manually annotated by BRENDA team
Niegowski, D.; Kleinschmidt, T.; Ahmad, S.; Qureshi, A.A.; Marback, M.; Rinaldo-Matthis, A.; Haeggstroem, J.Z.
Structure and inhibition of mouse leukotriene C4 synthase
PLoS ONE
9
e96763
2014
Mus musculus (Q60860), Mus musculus
Manually annotated by BRENDA team