Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein
AD Ferguson, BM McKeever, S Xu, D Wisniewski… - Science, 2007 - science.org
AD Ferguson, BM McKeever, S Xu, D Wisniewski, DK Miller, TT Yamin, RH Spencer, L Chu…
Science, 2007•science.orgLeukotrienes 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 …
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 …
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.
AAAS