Title
The structure of human 15-lipoxygenase-2 with a substrate mimic
Document Type
Article
Publication Date
3-21-2014
Abstract
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 Ca(2+)-binding sites that confer Ca(2+)-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.
Publication Source (Journal or Book title)
The Journal of biological chemistry
First Page
8562
Last Page
9
Recommended Citation
Kobe, M. J., Neau, D. B., Mitchell, C. E., Bartlett, S. G., & Newcomer, M. E. (2014). The structure of human 15-lipoxygenase-2 with a substrate mimic. The Journal of biological chemistry, 289 (12), 8562-9. https://doi.org/10.1074/jbc.M113.543777