- Crystal structure of a lipoxygenase in complex with substrate: The arachidonic acid-binding site of 8R-lipoxygenase
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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 ? 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.
- Neau, David B.,Bender, Gunes,Boeglin, William E.,Bartlett, Sue G.,Brash, Alan R.,Newcomer, Marcia E.
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p. 31905 - 31913
(2015/02/19)
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- Physcomitrella patens has lipoxygenases for both eicosanoid and octadecanoid pathways
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Mosses have substantial amounts of long chain C20 polyunsaturated fatty acids, such as arachidonic and eicosapentaenoic acid, in addition to the shorter chain C18 α-linolenic and linoleic acids, which are typical substrates of lipoxygenases in flowering p
- Anterola, Aldwin,G?bel, Cornelia,Hornung, Ellen,Sellhorn, George,Feussner, Ivo,Grimes, Howard
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experimental part
p. 40 - 52
(2009/07/11)
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- Production of hydroxy unsaturated fatty acids using crude lipoxygenase obtained from infected rice plants
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In order to explore the oxidation mode of lipoxygenase (LOX) obtained from infected rice plants, typical unsaturated fatty acids (3-8) were treated with LOX and oxygen. It was observed that ω-10 and ω-6 positions of unsaturated fatty acids were oxidized predominantly in the cases of exotic ω-6 (4 and 5) and ω-3 (7 and 8) series, respectively. In the case of endogenous fatty acids (3 and 6), oxidation at ω-6 position predominated. All the allylic alcohols obtained by reduction of the oxidation products with NaBH4 possess S-configuration.
- Kato, Tadahiro,Watanabe, Tsutomu,Hirukawa, Toshifumi,Tomita, Norihiro,Namai, Tsuneo
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p. 1663 - 1666
(2007/10/03)
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