4QWT

Anaerobic crystal structure of delta413-417:GS LOX in complex with arachidonate

4QWT の概要

• エントリーDOI: 10.2210/pdb4qwt/pdb
• 関連するPDBエントリー: 2FNQ 3FG3 3FG4 3FGI
• 分子名称: Allene oxide synthase-lipoxygenase protein, FE (II) ION, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: iron binding, membrane-associated, oxidoreductase
• 由来する生物種: Plexaura homomalla (black sea rod)
• 細胞内の位置: Cytoplasm : O16025
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 321738.85

構造登録者

Neau, D.B.,Newcomer, M.E. (登録日: 2014-07-17, 公開日: 2014-09-24, 最終更新日: 2023-09-20)

主引用文献

Neau, D.B.,Bender, G.,Boeglin, W.E.,Bartlett, S.G.,Brash, A.R.,Newcomer, M.E.
Crystal Structure of a Lipoxygenase in Complex with Substrate: THE ARACHIDONIC ACID-BINDING SITE OF 8R-LIPOXYGENASE.
J.Biol.Chem., 289:31905-31913, 2014

PubMed Abstract: Lipoxygenases (LOX) play critical roles in mammalian biology in the generation of potent lipid mediators of the inflammatory response; consequently, they are targets for the development of isoform-specific inhibitors. The regio- and stereo-specificity of the oxygenation of polyunsaturated fatty acids by the enzymes is understood in terms of the chemistry, but structural observation of the enzyme-substrate interactions is lacking. Although several LOX crystal structures are available, heretofore the rapid oxygenation of bound substrate has precluded capture of the enzyme-substrate complex, leaving a gap between chemical and structural insights. In this report, we describe the 2.0 Å resolution structure of 8R-LOX in complex with arachidonic acid obtained under anaerobic conditions. Subtle rearrangements, primarily in the side chains of three amino acids, allow binding of arachidonic acid in a catalytically competent conformation. Accompanying experimental work supports a model in which both substrate tethering and cavity depth contribute to positioning the appropriate carbon at the catalytic machinery.

PubMed: 25231982
DOI: 10.1074/jbc.M114.599662

実験手法

X-RAY DIFFRACTION (2.002 Å)