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The structure of human 15-lipoxygenase-2 with a substrate mimic.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2014 Mar 21; Vol. 289 (12), pp. 8562-9. Date of Electronic Publication: 2014 Feb 04. - Publication Year :
- 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.
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 289
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24497644
- Full Text :
- https://doi.org/10.1074/jbc.M113.543777