IED Industry Enzyme Database

Detail Information for IndEnz0002002180
IED ID IndEnz0002002180
Enzyme Type ID protease002180
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 LTA4
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 MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDLTIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLTPEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETPDPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETESMLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISHSWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGETHPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSITTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAKEDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWLRLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVTAMLVGKDLKVD
Enzyme Length 611
Uniprot Accession Number P09960
Absorption
Active Site ACT_SITE 297; /note="Proton acceptor"; /evidence="ECO:0000269|PubMed:11675384, ECO:0000305|PubMed:12207002, ECO:0000305|PubMed:24591641, ECO:0007744|PDB:1H19"; ACT_SITE 384; /note="Proton donor"; /evidence="ECO:0000269|PubMed:11675384, ECO:0000305|PubMed:12207002, ECO:0000305|PubMed:24591641, ECO:0007744|PDB:1H19"
Activity Regulation ACTIVITY REGULATION: Inhibited by bestatin (PubMed:11175901). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:7667299). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (PubMed:24591641). {ECO:0000269|PubMed:11175901, ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:7667299}.
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:11675384, ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:6490615, ECO:0000269|PubMed:7667299, ECO:0000269|PubMed:9395533};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22325; Evidence={ECO:0000305|PubMed:11917124}; 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:0000269|PubMed:21206090};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50273; Evidence={ECO:0000305|PubMed:21206090}; 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:0000269|PubMed:21206090};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51989; Evidence={ECO:0000305|PubMed:21206090}; CATALYTIC ACTIVITY: Reaction=Release of the N-terminal residue from a tripeptide.; EC=3.4.11.4; Evidence={ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:24591641, ECO:0000269|PubMed:9395533};
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. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the proinflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:20813919, PubMed:18804029). 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) (PubMed:20813919, PubMed:24591641). 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 (PubMed:21206090). {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:2244921, ECO:0000269|PubMed:24591641}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis. {ECO:0000269|PubMed:11917124}.
nucleotide Binding
Features Active site (2); Alternative sequence (3); Beta strand (25); Chain (1); Helix (32); Initiator methionine (1); Metal binding (3); Modified residue (5); Mutagenesis (27); Natural variant (1); Region (4); Sequence conflict (5); Site (4); Turn (8)
Keywords 3D-structure;Acetylation;Alternative splicing;Cytoplasm;Direct protein sequencing;Hydrolase;Leukotriene biosynthesis;Lipid metabolism;Metal-binding;Metalloprotease;Phosphoprotein;Protease;Reference proteome;Zinc
Interact With Q9BSI4
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:6490615}.
Modified Residue MOD_RES 73; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 337; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 414; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 416; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:9395533; MOD_RES 573; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861
Post Translational Modification PTM: Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity. {ECO:0000269|PubMed:9395533}.
Signal Peptide
Structure 3D X-ray crystallography (66)
Cross Reference PDB 1GW6; 1H19; 1HS6; 1SQM; 2R59; 2VJ8; 3B7R; 3B7S; 3B7T; 3B7U; 3CHO; 3CHP; 3CHQ; 3CHR; 3CHS; 3FH5; 3FH7; 3FH8; 3FHE; 3FTS; 3FTU; 3FTV; 3FTW; 3FTX; 3FTY; 3FTZ; 3FU0; 3FU3; 3FU5; 3FU6; 3FUD; 3FUE; 3FUF; 3FUH; 3FUI; 3FUJ; 3FUK; 3FUL; 3FUM; 3FUN; 3U9W; 4DPR; 4L2L; 4MKT; 4MS6; 4R7L; 4RSY; 4RVB; 5AEN; 5BPP; 5FWQ; 5N3W; 5NI2; 5NI4; 5NI6; 5NIA; 5NID; 5NIE; 6ENB; 6ENC; 6END; 6O5H; 7AUZ; 7AV0; 7AV1; 7AV2;
Mapped Pubmed ID 11739132; 12391014; 12590139; 15886380; 16169070; 16282974; 16293801; 16424216; 16698924; 17244615; 17353931; 17357161; 18318662; 18323512; 18394906; 18547289; 18599387; 19056482; 19130089; 19131661; 19214143; 19622707; 19865173; 19913121; 19919819; 19950900; 20067482; 20211140; 20237496; 20432426; 20562859; 20628086; 20711500; 20810156; 21044950; 21112816; 21867913; 22206291; 22848428; 23079278; 23153620; 23438748; 23573270; 23650620; 23828562; 24573245; 25625859; 25721704; 25799317; 26743932; 27126280; 27643598; 27651294; 28303931; 28419315; 28419368; 28827365; 28980694; 29051536; 2995393; 30352167; 30678701; 30745237; 30791695; 31093505; 31287215; 31751136; 32580506; 33329520; 33592148; 34595756;
Motif
Gene Encoded By
Mass 69,285
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.29 mM for Pro-Gly-Pro {ECO:0000269|PubMed:20813919};
Metal Binding METAL 296; /note="Zinc; catalytic"; /evidence="ECO:0000269|PubMed:11175901, ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:19618939, ECO:0000269|PubMed:24591641, ECO:0007744|PDB:1GW6, ECO:0007744|PDB:1H19, ECO:0007744|PDB:1HS6, ECO:0007744|PDB:1SQM, ECO:0007744|PDB:2R59, ECO:0007744|PDB:2VJ8, ECO:0007744|PDB:3B7R, ECO:0007744|PDB:3B7S, ECO:0007744|PDB:3B7T, ECO:0007744|PDB:3B7U, ECO:0007744|PDB:3CHO, ECO:0007744|PDB:3CHP, ECO:0007744|PDB:3CHQ, ECO:0007744|PDB:3CHR, ECO:0007744|PDB:3CHS, ECO:0007744|PDB:3FH5, ECO:0007744|PDB:3FH7, ECO:0007744|PDB:3FH8, ECO:0007744|PDB:3FHE, ECO:0007744|PDB:3FTS, ECO:0007744|PDB:3FTU, ECO:0007744|PDB:3FTV, ECO:0007744|PDB:3FTW, ECO:0007744|PDB:3FTX, ECO:0007744|PDB:3FTY, ECO:0007744|PDB:3FTZ, ECO:0007744|PDB:3FU0, ECO:0007744|PDB:3FU3, ECO:0007744|PDB:3FU5, ECO:0007744|PDB:3FU6, ECO:0007744|PDB:3FUD, ECO:0007744|PDB:3FUE, ECO:0007744|PDB:3FUF, ECO:0007744|PDB:3FUH, ECO:0007744|PDB:3FUI, ECO:0007744|PDB:3FUJ, ECO:0007744|PDB:3FUK, ECO:0007744|PDB:3FUL, ECO:0007744|PDB:3FUM, ECO:0007744|PDB:3FUN, ECO:0007744|PDB:3U9W, ECO:0007744|PDB:4DPR, ECO:0007744|PDB:4L2L, ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6, ECO:0007744|PDB:5AEN"; METAL 300; /note="Zinc; catalytic"; /evidence="ECO:0000269|PubMed:11175901, ECO:0000269|PubMed:11675384, ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:19618939, ECO:0000269|PubMed:24591641, ECO:0007744|PDB:1GW6, ECO:0007744|PDB:1H19, ECO:0007744|PDB:1HS6, ECO:0007744|PDB:1SQM, ECO:0007744|PDB:2R59, ECO:0007744|PDB:2VJ8, ECO:0007744|PDB:3B7R, ECO:0007744|PDB:3B7S, ECO:0007744|PDB:3B7T, ECO:0007744|PDB:3B7U, ECO:0007744|PDB:3CHO, ECO:0007744|PDB:3CHP, ECO:0007744|PDB:3CHQ, ECO:0007744|PDB:3CHR, ECO:0007744|PDB:3CHS, ECO:0007744|PDB:3FH5, ECO:0007744|PDB:3FH7, ECO:0007744|PDB:3FH8, ECO:0007744|PDB:3FHE, ECO:0007744|PDB:3FTS, ECO:0007744|PDB:3FTU, ECO:0007744|PDB:3FTV, ECO:0007744|PDB:3FTW, ECO:0007744|PDB:3FTX, ECO:0007744|PDB:3FTY, ECO:0007744|PDB:3FTZ, ECO:0007744|PDB:3FU0, ECO:0007744|PDB:3FU3, ECO:0007744|PDB:3FU5, ECO:0007744|PDB:3FU6, ECO:0007744|PDB:3FUD, ECO:0007744|PDB:3FUE, ECO:0007744|PDB:3FUF, ECO:0007744|PDB:3FUH, ECO:0007744|PDB:3FUI, ECO:0007744|PDB:3FUJ, ECO:0007744|PDB:3FUK, ECO:0007744|PDB:3FUL, ECO:0007744|PDB:3FUM, ECO:0007744|PDB:3FUN, ECO:0007744|PDB:3U9W, ECO:0007744|PDB:4DPR, ECO:0007744|PDB:4L2L, ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6, ECO:0007744|PDB:5AEN"; METAL 319; /note="Zinc; catalytic"; /evidence="ECO:0000269|PubMed:11175901, ECO:0000269|PubMed:24591641, ECO:0007744|PDB:1GW6, ECO:0007744|PDB:1H19, ECO:0007744|PDB:1HS6, ECO:0007744|PDB:1SQM, ECO:0007744|PDB:2R59, ECO:0007744|PDB:2VJ8, ECO:0007744|PDB:3B7R, ECO:0007744|PDB:3B7S, ECO:0007744|PDB:3B7T, ECO:0007744|PDB:3B7U, ECO:0007744|PDB:3CHO, ECO:0007744|PDB:3CHP, ECO:0007744|PDB:3CHQ, ECO:0007744|PDB:3CHR, ECO:0007744|PDB:3CHS, ECO:0007744|PDB:3FH5, ECO:0007744|PDB:3FH7, ECO:0007744|PDB:3FH8, ECO:0007744|PDB:3FHE, ECO:0007744|PDB:3FTS, ECO:0007744|PDB:3FTU, ECO:0007744|PDB:3FTV, ECO:0007744|PDB:3FTW, ECO:0007744|PDB:3FTX, ECO:0007744|PDB:3FTY, ECO:0007744|PDB:3FTZ, ECO:0007744|PDB:3FU0, ECO:0007744|PDB:3FU3, ECO:0007744|PDB:3FU5, ECO:0007744|PDB:3FU6, ECO:0007744|PDB:3FUD, ECO:0007744|PDB:3FUE, ECO:0007744|PDB:3FUF, ECO:0007744|PDB:3FUH, ECO:0007744|PDB:3FUI, ECO:0007744|PDB:3FUJ, ECO:0007744|PDB:3FUK, ECO:0007744|PDB:3FUL, ECO:0007744|PDB:3FUM, ECO:0007744|PDB:3FUN, ECO:0007744|PDB:3U9W, ECO:0007744|PDB:4DPR, ECO:0007744|PDB:4L2L, ECO:0007744|PDB:4MKT, ECO:0007744|PDB:4MS6, ECO:0007744|PDB:5AEN"
Rhea ID RHEA:22324; RHEA:22325; RHEA:50272; RHEA:50273; RHEA:51988; RHEA:51989
Cross Reference Brenda 3.3.2.6;3.4.11.6;