title: Structural basis for the positional specificity of lipoxygenases.
abstract: The positional specificity of arachidonic acid oxygenation is currently the decisive parameter for classification of mammalian lipoxygenases but, unfortunately, the structural reasons for lipoxygenase specificity are not well understood. Although there are no direct structural data on lipoxygenase/substrate interaction, experiments with modified fatty acid substrates and mutagenesis studies suggest that for 12- and 15-lipoxygenases, arachidonic acid slides into the substrate-binding pocket with its methyl end ahead. For arachidonate 5- and/or 8-lipoxygenation two alternative models for the enzyme/substrate interaction have been developed: 1) The orientation-determined model and 2) the space-determined model. This review explores the experimental data available on the mechanistic reasons for lipoxygenase specificity and concludes that each of the above-mentioned hypotheses may be valid for arachidonate 5-lipoxygenation under certain circumstances.
authors.affiliation: Institute of Biochemistry, University Clinics Charite, Humboldt University, Hessische Str. 3-4, 10 115., Berlin, F.R, Germany. hartmut.kuehn@charite.de
authors.forename: H
authors.initials: H
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D005227:Fatty Acids / Q000737:chemistry*; D006420:Hemeproteins; D008084:Lipoxygenase / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013379:Substrate Specificity
chemical_list: D005227:Fatty Acids; D006420:Hemeproteins; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase