title: Structural determinants of reductive terpene cyclization in iridoid biosynthesis.
abstract: The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound to a mechanism-inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. Key features that distinguish iridoid synthase from its close homolog progesterone 5β-reductase are highlighted.
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Hajo
authors.initials: H
authors.lastname: Kries
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Caputi
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Clare E M
authors.initials: CEM
authors.lastname: Stevenson
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Mohammed O
authors.initials: MO
authors.lastname: Kamileen
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Sherden
authors.affiliation: University of Copenhagen, Department of Plant and Environmental Sciences, Copenhagen Plant Science Centre & Section for Plant Biochemistry, Thorvaldsensvej 40, Copenhagen, Denmark.
authors.forename: Fernando
authors.initials: F
authors.lastname: Geu-Flores
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Lawson
authors.affiliation: The John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: O'Connor
mesh_terms: D030008:Catharanthus / Q000201:enzymology*; D018360:Crystallography, X-Ray; D003500:Cyclization; D039823:Iridoids / Q000378:metabolism*; D008958:Models, Molecular; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D039823:Iridoids; D010940:Plant Proteins; D013729:Terpenes; D010088:Oxidoreductases; C090493:progesterone 5 beta-reductase