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 (see EC 3.4.11.6, aminopeptidase B). It also converts leukotriene A4 into leukotriene B4, unlike EC 3.3.2.10, 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) .
His295, His299, Glu318, Glu271 are amino acids involved in metallic binding and epoxid hydrolase activity, additional Glu296 and Tyr383 are required for the aminopeptidase activity
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 3.3.2.10, 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) [5].
mutants of Tyr378 are able to generate, not only leukotriene B4, but also (5S,12R)-dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, in a yield of about 20-30%
the aminopeptidase activity accepts a variety of substrates and certain arginyl di- and tri-peptides as well as p-nitroanilide derivates of Ala and Arg
isolated from Streptomyces olivoreticuli, a general AP inhibitor, inhibits LTB4 biosynthesis. Following a short-term intraperitoneal treatment with 10 mg/kg bestatin, LTB4 biosynthesis in the esophagoduodenal junction is significantly suppressed in rats treated with EGDA compared to that in the untreated group, in an esophagogastroduodenal anastomosis (EGDA) surgical model. Bestatin inhibits LTA4H/LTB4 activation and reduces tumorigenesis in EGDA rats
LTA4H is overexpressed in all rat esophageal adenocarcinoma (EAC) samples compared to that in the normal duodenal tissues in an esophagogastroduodenal anastomosis (EGDA) surgical model
enzyme leukotriene A4 hydrolase (LTA4H) is characterized as a bifunctional enzyme with epoxide hydrolase (EH) and aminopeptidase (AP) activities. LTA4H plays a critical role in modulating inflammation by producing LTB4 via its EH activity. LTA4H also has putative roles in cancer development
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
LTA4H is overexpressed in all rat esophageal adenocarcinoma (EAC) samples compared to that in the normal duodenal tissues in an esophagogastroduodenal anastomosis (EGDA) surgical model
enzyme overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of esophageal adenocarcinogenesis
the product is a classical chemoattractant, triggers adherence and aggregation of leukocytes to the endothelium, modulates immune responses, participates in the host-defence against infections and is a mediator of PAF-induced lethal shock
Brock, T.G.; Maydanski, E.; McNish, R.W.; Peters-Golden, M.
Co-localization of leukotriene A4 hydrolase with 5-lipoxygenase in nuclei of alveolar macrophages and rat basophilic leukemia cells but not neutrophils