| 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; |