Functional Properties and Molecular Architecture of Leukotriene A4 Hydrolase, a Pivotal Catalyst of Chemotactic Leukotriene Formation

Abstract

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 of the function and molecular architecture of leukotriene A₄ hydrolase.