2Q7M

Crystal structure of human FLAP with MK-591

2Q7M の概要

• エントリーDOI: 10.2210/pdb2q7m/pdb
• 関連するPDBエントリー: 2Q7R
• 分子名称: Arachidonate 5-lipoxygenase-activating protein, 3-[3-(TERT-BUTYLTHIO)-1-(4-CHLOROBENZYL)-5-(QUINOLIN-2-YLMETHOXY)-1H-INDOL-2-YL]-2,2-DIMETHYLPROPANOIC ACID (2 entities in total)
• 機能のキーワード: mapeg, membrane protein, flap, lipid transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus membrane; Multi-pass membrane protein: P20292
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 112194.49

構造登録者

Ferguson, A.D. (登録日: 2007-06-07, 公開日: 2007-08-21, 最終更新日: 2024-02-21)

主引用文献

Ferguson, A.D.,McKeever, B.M.,Xu, S.,Wisniewski, D.,Miller, D.K.,Yamin, T.T.,Spencer, R.H.,Chu, L.,Ujjainwalla, F.,Cunningham, B.R.,Evans, J.F.,Becker, J.W.
Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein.
Science, 317:510-512, 2007

PubMed 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.

PubMed: 17600184
DOI: 10.1126/science.1144346

実験手法

X-RAY DIFFRACTION (4.25 Å)