A comprehensive model of positional and stereo control in lipoxygenases.
The lipoxygenase gene family can synthesize an array of chiral hydroperoxy derivatives from polyunsaturated fatty acids. An individual enzyme, however, reacts molecular oxygen on a single position on the carbon chain and in a single stereo configuration. Regiospecificity is regulated by the orientation and depth of substrate entry into the active site. Stereospecificity is a different issue and only recently has experimental support emerged to explain the conceptual basis of stereo control. A key determinant is a single active site residue conserved as an Ala in S lipoxygenases and a Gly in R lipoxygenases; this residue controls R or S stereochemistry by switching the position of oxygenation on the reacting pentadiene of the substrate. In this review, we meld together the factors that control product regio- and stereochemistry into a general model that can account for the specificity of individual lipoxygenase reactions.
Coffa
Gianguido
G
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Schneider
Claus
C
Brash
Alan R
AR
D000818:Animals; D006801:Humans; D008084:Lipoxygenase / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity
D008084:Lipoxygenase