105500-09-2Relevant academic research and scientific papers
Crystal structure of a lipoxygenase in complex with substrate: The arachidonic acid-binding site of 8R-lipoxygenase
Neau, David B.,Bender, Gunes,Boeglin, William E.,Bartlett, Sue G.,Brash, Alan R.,Newcomer, Marcia E.
, p. 31905 - 31913 (2014)
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.
ENANTIOSPECIFIC TOTAL SYNTHESIS OF 8- and 12-HYDROXYEICOSATETRAENOIC ACID
Yadagiri, Pendri,Lumin, Sun,Mosset, Paul,Capdevila, Jorge,Falck, J. R.
, p. 6039 - 6040 (2007/10/02)
The R- and S-isomers of 8- and 12-hidroxyeicosatetraenoic acid (8- and 12-HETE) were synthesized from dimethyl malate derived precursors.
