EC 3.3.2.6 - Leukotriene-A4 hydrolase

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IntEnz Enzyme Nomenclature
EC 3.3.2.6

Names

Accepted name:
leukotriene-A4 hydrolase
Other names:
LTA4H
LTA4 hydrolase
LTA-4 hydrolase
leukotriene A4 hydrolase
Systematic name:
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase

Reaction

Cofactor

Comments:

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-eicosatetraenoic 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].

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00129
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004463
CAS Registry Number: 90119-07-6
UniProtKB/Swiss-Prot: (39) [show] [UniProt]

References

  1. Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W.
    Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils.
    Biochim. Biophys. Acta 840: 43-50 (1985). [PMID: 3995081]
  2. Minami, M., Ohno, S., Kawasaki, H., Rådmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T., Seyama, Y. and 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: 13873-13876 (1987). [PMID: 3654641]
  3. Haeggström, J., Meijer, J. and Rådmark, 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: 6332-6337 (1986). [PMID: 3009453]
  4. Newman, J.W., Morisseau, C. and Hammock, B.D.
    Epoxide hydrolases: their roles and interactions with lipid metabolism.
    Prog. Lipid Res. 44: 1-51 (2005). [PMID: 15748653]
  5. Fretland, A.J. and Omiecinski, C.J.
    Epoxide hydrolases: biochemistry and molecular biology.
    Chem. Biol. Interact. 129: 41-59 (2000). [PMID: 11154734]
  6. Orning, L., Gierse, J.K. and Fitzpatrick, F.A.
    The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity.
    J. Biol. Chem. 269: 11269-11273 (1994). [PMID: 8157657]
  7. Ohishi, N., Izumi, T., Minami, M., Kitamura, S., Seyama, Y., Ohkawa, S., Terao, S., Yotsumoto, H., Takaku, F. and Shimizu, T.
    Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers.
    J. Biol. Chem. 262: 10200-10205 (1987). [PMID: 3038871]

[EC 3.3.2.6 created 1989, modified 2006]