Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein.
Science
; 317(5837): 510-2, 2007 Jul 27.
Article
em En
| MEDLINE
| ID: mdl-17600184
ABSTRACT
Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.
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Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Proteínas de Transporte
/
Indóis
/
Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article