Detail Information for IndEnz0018000620
IED ID IndEnz0018000620
Enzyme Type ID peroxidase000620
Protein Name Leukotriene C4 synthase
LTC4 synthase
EC 4.4.1.20
Glutathione S-transferase LTC4
EC 2.5.1.-
Leukotriene-C
4
synthase
Leukotriene-C4 synthase
Gene Name LTC4S
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MKDEVALLAAVTLLGVLLQAYFSLQVISARRAFRVSPPLTTGPPEFERVYRAQVNCSEYFPLFLATLWVAGIFFHEGAAALCGLVYLFARLRYFQGYARSAQLRLAPLYASARALWLLVALAALGLLAHFLPAALRAALLGRLRTLLPWA
Enzyme Length 150
Uniprot Accession Number Q16873
Absorption
Active Site ACT_SITE 31; /note=Proton donor; /evidence=ECO:0000305|PubMed:17632548; ACT_SITE 104; /note=Proton acceptor; /evidence=ECO:0000305|PubMed:17632548
Activity Regulation ACTIVITY REGULATION: Inhibited by MK886. {ECO:0000269|PubMed:27791009}.
Binding Site BINDING 30; /note="Glutathione"; /evidence="ECO:0000269|PubMed:17632546, ECO:0000269|PubMed:17632548, ECO:0000269|PubMed:27365393"
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=leukotriene C4 = glutathione + leukotriene A4; Xref=Rhea:RHEA:17617, ChEBI:CHEBI:57463, ChEBI:CHEBI:57925, ChEBI:CHEBI:57973; EC=4.4.1.20; Evidence={ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27365393, ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7937884, ECO:0000269|PubMed:9153254};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17619; Evidence={ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27365393, ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7937884, ECO:0000269|PubMed:9153254}; CATALYTIC ACTIVITY: Reaction=(13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + glutathione = (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate; Xref=Rhea:RHEA:53508, ChEBI:CHEBI:57925, ChEBI:CHEBI:131958, ChEBI:CHEBI:137407; Evidence={ECO:0000269|PubMed:27791009};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53509; Evidence={ECO:0000305|PubMed:27791009};
DNA Binding
EC Number 4.4.1.20; 2.5.1.-
Enzyme Function FUNCTION: Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4 with high specificity (PubMed:7937884, PubMed:27791009, PubMed:27365393, PubMed:9153254, PubMed:23409838). Can also catalyzes the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions (PubMed:27791009). {ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27365393, ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7937884, ECO:0000269|PubMed:9153254}.
Temperature Dependency
PH Dependency BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8. {ECO:0000269|PubMed:9153254};
Pathway PATHWAY: Lipid metabolism; leukotriene C4 biosynthesis. {ECO:0000305}.
nucleotide Binding
Features Active site (2); Binding site (1); Chain (1); Helix (5); Modified residue (1); Mutagenesis (7); Natural variant (1); Region (3); Sequence conflict (1); Topological domain (5); Transmembrane (4)
Keywords 3D-structure;Direct protein sequencing;Endoplasmic reticulum;Leukotriene biosynthesis;Lipid biosynthesis;Lipid metabolism;Lyase;Membrane;Nucleus;Phosphoprotein;Reference proteome;Transferase;Transmembrane;Transmembrane helix
Interact With P11912; Q96BA8; Q15125; O14843; Q14802-3; Q8TDT2; O15529; Itself; Q8TBB6; Q4KMG9
Induction
Subcellular Location SUBCELLULAR LOCATION: Nucleus outer membrane {ECO:0000269|PubMed:12023288}; Multi-pass membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:12023288, ECO:0000269|PubMed:19233132}; Multi-pass membrane protein. Nucleus membrane {ECO:0000269|PubMed:19233132}; Multi-pass membrane protein.
Modified Residue MOD_RES 36; /note=Phosphoserine; by RPS6KB1; /evidence=ECO:0000269|PubMed:27365393
Post Translational Modification PTM: Phosphorylation at Ser-36 by RPS6KB1 inhibits the leukotriene-C4 synthase activity. {ECO:0000269|PubMed:27365393}.
Signal Peptide
Structure 3D X-ray crystallography (16)
Cross Reference PDB 2PNO; 2UUH; 2UUI; 3B29; 3HKK; 3LEO; 3PCV; 4BPM; 4J7T; 4J7Y; 4JC7; 4JCZ; 4JRZ; 4WAB; 5HV9; 6R7D;
Mapped Pubmed ID 10830912; 10887308; 11739132; 11770699; 12063521; 12360108; 12728163; 12968987; 14749922; 15131571; 16211251; 16340173; 16730545; 17110605; 17291864; 17460547; 18184802; 18647347; 19862937; 20980252; 21454538; 22139193; 24366866; 24803849; 25324525; 25506719; 25713027; 26881986; 3006030; 3118366; 31415176; 3164719; 3579953; 3770188; 6089195; 6422933; 7568157; 9393345;
Motif
Gene Encoded By
Mass 16,567
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=70 uM for glutathione {ECO:0000269|PubMed:27365393}; KM=300 uM for glutathione {ECO:0000269|PubMed:23409838}; KM=30 uM for leukotriene A4 {ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27791009}; KM=70.5 uM for 13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid {ECO:0000269|PubMed:27791009}; KM=76 uM for leukotriene A4 {ECO:0000269|PubMed:27365393}; Vmax=70.5 mmol/min/mg enzyme with 13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid as substrate {ECO:0000269|PubMed:27791009}; Vmax=6.7 mmol/min/mg enzyme with leukotriene A4 as substrate {ECO:0000269|PubMed:27791009}; Note=kcat is 19 sec(-1) with glutathione as substrate (PubMed:27365393). kcat is 105 sec(-1) with leukotriene A4 as substrate (PubMed:27365393). {ECO:0000269|PubMed:27365393};
Metal Binding
Rhea ID RHEA:17617; RHEA:17619; RHEA:53508; RHEA:53509
Cross Reference Brenda 4.4.1.20;