title: A comprehensive model of positional and stereo control in lipoxygenases.
abstract: 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.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Gianguido
authors.initials: G
authors.lastname: Coffa
authors.forename: Claus
authors.initials: C
authors.lastname: Schneider
authors.forename: Alan R
authors.initials: AR
authors.lastname: Brash
mesh_terms: D000818:Animals; D006801:Humans; D008084:Lipoxygenase / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D008084:Lipoxygenase