4nre

Publication Abstract from PubMed

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.

The structure of human 15-lipoxygenase-2 with a substrate mimic.,Kobe MJ, Neau DB, Mitchell CE, Bartlett SG, Newcomer ME J Biol Chem. 2014 Mar 21;289(12):8562-9. doi: 10.1074/jbc.M113.543777. Epub 2014 , Feb 4. PMID:24497644^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.