title: The Thr-His Connection on the Distal Heme of Catalase-Related Hemoproteins: A Hallmark of Reaction with Fatty Acid Hydroperoxides.
abstract: This review focuses on a group of heme peroxidases that retain the catalase fold in structure, yet show little or no reaction with hydrogen peroxide. Instead of having a role in oxidative defense, these enzymes are involved in secondary metabolite biosynthesis. The prototypical enzyme is catalase-related allene oxide synthase, an enzyme that converts a specific fatty acid hydroperoxide to the corresponding allene oxide (epoxide). Other catalase-related enzymes form allylic epoxides, aldehydes, or a bicyclobutane fatty acid. In all catalases (including these relatives), a His residue on the distal face of the heme is absolutely required for activity. Its immediate neighbor in sequence as well as in 3 D space is conserved as Val in true catalases and Thr in the fatty acid hydroperoxide-metabolizing enzymes. Thr-His on the distal face of the heme is critical in switching the substrate specificity from H2O2to fatty acid hydroperoxide.
authors.affiliation: Department of Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mashhadi
authors.affiliation: Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, 70803, USA.
authors.forename: Marcia E
authors.initials: ME
authors.lastname: Newcomer
authors.affiliation: Department of Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. alan.brash@vanderbilt.edu.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Brash
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D006420:Hemeproteins; D006859:Hydrogen; D002374:Catalase
keywords: allene oxide synthase; biosynthesis; catalase; fatty acid peroxides; heme proteins