title: Leukotriene A4 hydrolase.
abstract: The leukotrienes (LTs) are a family of lipid mediators involved in inflammation and allergy. Leukotriene B4 is a classical chemoattractant, which triggers adherence and aggregation of leukocytes to the endothelium at only nanomolar concentrations. In addition, leukotriene B4 modulates immune responses, participates in the host-defense against infections, and is a key mediator of PAF-induced lethal shock. Because of these powerful biological effects, leukotriene B4 is implicated in a variety of acute and chronic inflammatory diseases, e.g. nephritis, arthritis, dermatitis, and chronic obstructive pulmonary disease. The final step in the biosynthesis of leukotriene B4 is catalyzed by leukotriene A4 hydrolase, a unique bi-functional zinc metalloenzyme with an anion-dependent aminopeptidase activity. Here we describe the most recent developments regarding our understanding of the structure, function, and catalytic mechanisms of leukotriene A4 hydrolase.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. jesper.haeggstrom@mbb.ki.se
authors.forename: Jesper Z
authors.initials: JZ
authors.lastname: Haeggström
authors.forename: Filippa
authors.initials: F
authors.lastname: Kull
authors.forename: Peter C
authors.initials: PC
authors.lastname: Rudberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Tholander
authors.forename: Marjolein M G M
authors.initials: MM
authors.lastname: Thunnissen
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D015289:Leukotrienes; D008024:Ligands; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase