title: IspG converts an epoxide substrate analogue to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate: implications for IspG catalysis in isoprenoid biosynthesis.
abstract: IspG is an intriguing enzyme in bacteria, parasite, and plant isoprenoid biosynthesis, and its catalytic mechanism remains elusive. We report here the synthesis of (2R,3R)-4-hydroxy-3-methyl-2,3-epoxybutanyl diphosphate (Epoxy-HMBPP), a proposed intermediate in one of the frequently cited mechanistic models. We have also demonstrated that this epoxide analogue is a catalytically competent IspG substrate. This study represents the first mechanistic study of this important enzyme.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Nyland
authors.forename: Youli
authors.initials: Y
authors.lastname: Xiao
authors.forename: Pinghua
authors.initials: P
authors.lastname: Liu
authors.forename: Caren L
authors.initials: CL
authors.lastname: Freel Meyers
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D055162:Biocatalysis; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism*; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: C547602:(E)-4-hydroxy-3-methylbut-2-enyl diphosphate; D004852:Epoxy Compounds; D009943:Organophosphorus Compounds; D013729:Terpenes; D019883:Alkyl and Aryl Transferases