Review Article TheScientificWorldJOURNAL (2002) 2, 1734–1749 ISSN 1537-744X; DOI 10.1100/tsw.2002.810 Functional Properties and Molecular Architecture of Leukotriene A4 Hydrolase, a Pivotal Catalyst of Chemotactic Leukotriene Formation Jesper Z. Haeggström1,*, Pär Nordlund2, and Marjolein M.G.M. Thunnissen2 1Department of Medical Biochemistry and Biophysics, Division of Chemistry 2, Karolinska Institutet, S-171 77 Stockholm, Sweden; 2Department of Biochemistry, University of Stockholm, Arrhenius Laboratories A4, S-106 91 Stockholm, Sweden E-mail:
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[email protected] Received March 25, 2002; Accepted April 26, 2002; Published June 26, 2002 The leukotrienes 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 nM 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 bifunctional zinc metalloenzyme with an anion-dependent aminopeptidase activity. Here we describe the most recent developments regarding our understanding