| Entry |
|
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| Name |
leukotriene-A4 hydrolase;
LTA4 hydrolase;
LTA4H;
leukotriene A4 hydrolase |
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| Class |
Hydrolases;
Acting on ether bonds;
Ether hydrolases
 |
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| Sysname |
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate
hydrolase |
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| Reaction(IUBMB) |
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O =
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
[RN:R03057] |
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| Reaction(KEGG) |
R03057
 |
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| Substrate |
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate
[CPD:C00909];
H2O [CPD:C00001] |
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| Product |
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
[CPD:C02165] |
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| Comment |
This is a bifunctional zinc metalloprotease that displays both
epoxide hydrolase and aminopeptidase activities [4,6]. It
preferentially cleaves tripeptides at an arginyl bond, with
dipeptides and tetrapeptides being poorer substrates [6] (see EC
3.4.11.6, aminopeptidase B). It also converts leukotriene A4 into
leukotriene B4, unlike EC 3.2.2.10, soluble epoxide hydrolase, which
converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic
acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been
identified to date: EC 3.3.2.6 (leukotriene A4 hydrolase), EC
3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal
epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC
3.3.2.11 (cholesterol-5,6-oxide hydrolase) [3]. |
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| Pathway |
PATH: ec00590 Arachidonic acid metabolism
PATH: ec01100 Metabolic pathways |
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| Orthology |
KO: K01254 leukotriene-A4 hydrolase |
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| Genes |
HSA: 4048(LTA4H)
PTR: 452145(LTA4H)
MMU: 16993(Lta4h)
RNO: 299732(Lta4h)
CFA: 482611(LTA4H)
BTA: 507130(LTA4H)
SSC: 100154219(LTA4H)
ECB: 100052257
MDO: 100017641
OAA: 100078821
GGA: 417918(LTA4H)
TGU: 100224355
XLA: 432332
XTR: 448745(lta4h)
DRE: 406575(lta4h)
CIN: 100176354
SPU: 592555
DME: Dmel_CG10602
DPO: Dpse_GA25817
DAN: Dana_GF20677
DER: Dere_GG21678
DPE: Dper_GL18827
DSE: Dsec_GM17056
DSI: Dsim_GD21803
DYA: Dyak_GE12699
DGR: Dgri_GH11524
DMO: Dmoj_GI17019
AGA: AgaP_AGAP009907
AAG: AaeL_AAEL003666
CQU: CpipJ_CPIJ011448
NVI: 100124119
TCA: 661729
API: 100162284
ISC: IscW_ISCW022724
CEL: ZC416.6(protease)
CBR: CBG08301
SMM: Smp_007550
NVE: NEMVE_v1g247046
HMG: 100211539
TAD: TRIADDRAFT_23795
ATH: AT5G13520
POP: POPTR_832515
RCU: RCOM_1071200
VVI: 100243305
OSA: 4334583(Os03g0819100)
SBI: SORBI_01g003380(SORBIDRAFT_01g003380)
CRE: CHLREDRAFT_113845(LKHA4)
SCE: YNL045W(LAP2)
AGO: AGOS_ADL233W
KLA: KLLA0F03883g
DHA: DEHA0B15070g
PIC: PICST_76777(LKA4) PICST_82220(LTA4)
PPA: PAS_chr2-1_0487
VPO: Kpol_1039p41
LEL: LELG_00410
ZRO: ZYRO0D02574g
CAL: CaO19.8607
CTP: CTRG_03303
CDU: CD36_09880
CGR: CAGL0G01430g
YLI: YALI0F00396g
SPO: SPCC1322.05c
NCR: NCU06732
PAN: PODANSg8894
MGR: MGG_09481
FGR: FG10188.1
ANI: AN5812.2
AFM: AFUA_2G07520
AOR: AO090011000940
ANG: An05g00070
AFV: AFLA_047330
PCS: Pc13g05400
NFI: NFIA_083260
CIM: CIMG_05732
SSL: SS1G_05513
BFU: BC1G_09514
CNE: CNE04600
CNB: CNBE4600
LBC: LACBIDRAFT_253885
MPR: MPER_02716 MPER_07004
MBR: MONBRDRAFT_33026
DDI: DDB_0191291(lkhA)
TET: TTHERM_00579060 TTHERM_00579070
PTM: GSPATT00005113001 GSPATT00020188001 GSPATT00027103001
GSPATT00032843001
PTI: PHATRDRAFT_13602
TPS: THAPSDRAFT_269777(LTA4)
 |
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| Structures |
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 |
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Reference
Authors
Title
Journal
Organism
|
1 [PMID:3995081]
Evans JF, Dupuis P, Ford-Hutchinson AW.
Purification and characterisation of leukotriene A4 hydrolase from
rat neutrophils.
Biochim. Biophys. Acta. 840 (1985) 43-50.
Rattus norvegicus [GN:rno] |
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Reference
Authors
Title
Journal
Organism
|
2 [PMID:3654641]
Minami M, Ohno S, Kawasaki H, Radmark O, Samuelsson B, Jornvall H,
Shimizu T, Seyama Y, Suzuki K.
Molecular cloning of a cDNA coding for human leukotriene A4
hydrolase. Complete primary structure of an enzyme involved in
eicosanoid synthesis.
J. Biol. Chem. 262 (1987) 13873-6.
Homo sapiens [GN:hsa] |
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Reference
Authors
Title
Journal
Organism
|
3 [PMID:3009453]
Haeggstrom J, Meijer J, Radmark O.
Leukotriene A4. Enzymatic conversion into
5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver
cytosolic epoxide hydrolase.
J. Biol. Chem. 261 (1986) 6332-7.
Mus musculus [GN:mmu] |
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Reference
Authors
Title
Journal
Organism
|
4 [PMID:15748653]
Newman JW, Morisseau C, Hammock BD.
Epoxide hydrolases: their roles and interactions with lipid
metabolism.
Prog. Lipid. Res. 44 (2005) 1-51.
Homo sapiens [GN:hsa], Mus musculus [GN:mmu], Rattus norvegicus
[GN:rno], Saccharomyces cerevisiae [GN:sce], Xenopus laevis |
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Reference
Authors
Title
Journal
Organism
|
5 [PMID:11154734]
Fretland AJ, Omiecinski CJ.
Epoxide hydrolases: biochemistry and molecular biology.
Chem. Biol. Interact. 129 (2000) 41-59.
Homo sapiens [GN:hsa] |
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Reference
Authors
Title
Journal
Organism
|
6 [PMID:8157657]
Orning L, Gierse JK, Fitzpatrick FA.
The bifunctional enzyme leukotriene-A4 hydrolase is an arginine
aminopeptidase of high efficiency and specificity.
J. Biol. Chem. 269 (1994) 11269-73.
Homo sapiens [GN:hsa], Mus musculus [GN:mmu] |
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Reference
Authors
Title
Journal
Organism
|
7 [PMID:3038871]
Ohishi N, Izumi T, Minami M, Kitamura S, Seyama Y, Ohkawa S, Terao
S, Yotsumoto H, Takaku F, Shimizu T.
Leukotriene A4 hydrolase in the human lung. Inactivation of the
enzyme with leukotriene A4 isomers.
J. Biol. Chem. 262 (1987) 10200-5.
Homo sapiens [GN:hsa] |
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| Other DBs |
ExplorEnz - The Enzyme Database: 3.3.2.6
IUBMB Enzyme Nomenclature: 3.3.2.6
ExPASy - ENZYME nomenclature database: 3.3.2.6
BRENDA, the Enzyme Database: 3.3.2.6
CAS: 90119-07-6 |
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