The structure of human 15-lipoxygenase-2 with a substrate mimic.
J Biol Chem
; 289(12): 8562-9, 2014 Mar 21.
Article
en En
| MEDLINE
| ID: mdl-24497644
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Araquidonato 15-Lipooxigenasa
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Estados Unidos