| IED ID | IndEnz0002002208 |
| Enzyme Type ID | protease002208 |
| Protein Name |
Leukotriene A-4 hydrolase LTA-4 hydrolase EC 3.3.2.6 Leukotriene A 4 hydrolase Tripeptide aminopeptidase LTA4H EC 3.4.11.4 |
| Gene Name | Lta4h |
| Organism | Rattus norvegicus (Rat) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MPEVADTCSLASPASVCRTQHLHLRCSVDFARRALTGTAALTVQSQEDNLRSLTLDTKDLTIEKVVINGQEVKYTLGESQGYKGSPMEISLPIALSKNQEVVIEISFETSPKSSALQWLTPEQTSGKQHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGEAPDPEDPSRKIYRFNQRVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETESMLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISHSWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFHALGGWGELQNTIKTFGESHPFTKLVVDLKDVDPDVAYSSIPYEKGFALLFYLEQLLGGPEVFLGFLKAYVEKFSYQSVTTDDWKSFLYAHFKDKVDLLNQVDWNAWLYAPGLPPVKPNYDVTLTNACIALSQRWVTAKEEDLNSFSIEDLKDLSSHQLNEFLAQVLQKAPLPLGHIKRMQEVYNFNAINNSEIRFRWLRLCIQSKWEEAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKACMHPVTAMLVGKDLKVD |
| Enzyme Length | 611 |
| Uniprot Accession Number | P30349 |
| Absorption | |
| Active Site | ACT_SITE 297; /note=Proton acceptor; /evidence=ECO:0000250|UniProtKB:P09960; ACT_SITE 384; /note=Proton donor; /evidence=ECO:0000250|UniProtKB:P09960 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by bestatin (By similarity). Inhibited by captopril (PubMed:1544505). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379. 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (By similarity). {ECO:0000250|UniProtKB:P09960, ECO:0000269|PubMed:1544505}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=H2O + leukotriene A4 = leukotriene B4; Xref=Rhea:RHEA:22324, ChEBI:CHEBI:15377, ChEBI:CHEBI:57461, ChEBI:CHEBI:57463; EC=3.3.2.6; Evidence={ECO:0000269|PubMed:1544505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22325; Evidence={ECO:0000305|PubMed:1544505}; CATALYTIC ACTIVITY: Reaction=(5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O = resolvin E1; Xref=Rhea:RHEA:50272, ChEBI:CHEBI:15377, ChEBI:CHEBI:91000, ChEBI:CHEBI:132219; Evidence={ECO:0000250|UniProtKB:P09960};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50273; Evidence={ECO:0000250|UniProtKB:P09960}; CATALYTIC ACTIVITY: Reaction=(5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O = 18S-resolvin E1; Xref=Rhea:RHEA:51988, ChEBI:CHEBI:15377, ChEBI:CHEBI:134661, ChEBI:CHEBI:136057; Evidence={ECO:0000250|UniProtKB:P09960};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51989; Evidence={ECO:0000250|UniProtKB:P09960}; CATALYTIC ACTIVITY: Reaction=Release of the N-terminal residue from a tripeptide.; EC=3.4.11.4; Evidence={ECO:0000250|UniProtKB:P09960}; |
| DNA Binding | |
| EC Number | 3.3.2.6; 3.4.11.4 |
| Enzyme Function | FUNCTION: Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities (By similarity). Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the proinflammatory mediator leukotriene B4 (LTB4) (PubMed:1544505). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides. In addition to its proinflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (By similarity). {ECO:0000250|UniProtKB:P09960, ECO:0000269|PubMed:1544505}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis. {ECO:0000269|PubMed:1544505}. |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Metal binding (3); Modified residue (5); Region (3); Sequence conflict (5); Site (2) |
| Keywords | Acetylation;Cytoplasm;Hydrolase;Leukotriene biosynthesis;Metal-binding;Metalloprotease;Phosphoprotein;Protease;Reference proteome;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P09960}. |
| Modified Residue | MOD_RES 73; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P09960; MOD_RES 337; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P09960; MOD_RES 414; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P09960; MOD_RES 416; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P09960; MOD_RES 573; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P09960 |
| Post Translational Modification | PTM: Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity. {ECO:0000250|UniProtKB:P09960}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10601658; 12865451; 15715933; 15805137; 17985342; 3995081; |
| Motif | |
| Gene Encoded By | |
| Mass | 69,089 |
| Kinetics | |
| Metal Binding | METAL 296; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:P09960; METAL 300; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:P09960; METAL 319; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:P09960 |
| Rhea ID | RHEA:22324; RHEA:22325; RHEA:50272; RHEA:50273; RHEA:51988; RHEA:51989 |
| Cross Reference Brenda | 3.3.2.6; |