Atherosclerosis is associated with chronic inflammation occurring over decades. The enzyme 15-lipoxygenase-2 (15-LOX-2) is highly expressed in large atherosclerotic plaques, and its activity has been linked to the progression of macrophages to the lipid-laden foam cells present in atherosclerotic plaques.We report here the crystal structure of human 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. The loop is flanked by two Ca2+-binding sites that confer Ca2+-dependent membrane binding. A comparison of the human 15-LOX-2 and 5-LOX structures reveals similarities at the active sites, as well striking differences that can be exploited for design of isoform-selective inhibitors. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication Source (Journal or Book title)
Journal of Biological Chemistry
Kobe, M., Neau, D., Mitchell, C., Bartlett, S., & Newcomer, M. (2014). The structure of human 15-lipoxygenase-2 with a substrate mimic. Journal of Biological Chemistry, 289 (12), 8562-8569. https://doi.org/10.1074/jbc.M113.543777