title: Lipoxygenase-catalyzed formation of R-configuration hydroperoxides.
abstract: Prototypical lipoxygenases (LOXs) of animals and plants synthesize hydroperoxy fatty acids of the S stereoconfiguration, yet enzymes forming R-configuration products are found in both the animal and plant kingdoms. R-LOX are widespread in aquatic invertebrates, in some of which their R-HETE products have a defined role in reproductive function. A 12R-LOX has been found recently in humans and mice. The human 12R-LOX product, 12R-HETE, appears to be involved in the pathophysiology of psoriasis and other proliferative skin diseases; a role in normal skin development is implied from the spatial and temporal expression patterns of the 12R-LOX in the mouse embryo. In plants, there are few reports of R-LOX activity and in higher plants this is limited to enzymes that catalyze a significant degree of non-specific oxygenation. There are no obvious amino acid sequence motifs characterizing R-LOXs; and in the phylogenetic tree of the LOX superfamily, the R-LOXs do not group into a specific branch of genes. The mechanistic basis of stereocontrol over the oxygenation reaction performed by LOXs may relate to a changed binding orientation of the fatty acid substrate or to the direction of attack by molecular oxygen. A potentially relevant precedent for switching of R- and S-oxygenation specificity was described recently in studies of prostaglandin C-15 oxygenation during cycloxygenase catalysis; single amino acid changes can invert the oxygenation stereospecificity at C-15. In this case, the evidence suggests that R/S switching can occur with the substrate binding in the normal conformation.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-6602, USA.
authors.forename: Claus
authors.initials: C
authors.lastname: Schneider
authors.forename: Alan R
authors.initials: AR
authors.lastname: Brash
mesh_terms: D000818:Animals; D002384:Catalysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism*; D008084:Lipoxygenase / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D010802:Phylogeny; D010940:Plant Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism
chemical_list: D010940:Plant Proteins; D006861:Hydrogen Peroxide; D008084:Lipoxygenase; D010100:Oxygen