title: Study of 1-deoxy-D-xylulose-5-phosphate reductoisomerase: synthesis and evaluation of fluorinated substrate analogues.
abstract: [reaction: see text] 1-deoxy-D-xylulose-5-phosphate (DXP) reductoisomerase is a NADPH-dependent enzyme catalyzing the conversion of DXP to methyl-D-erythritol 4-phosphate (MEP). In this study, each of the hydroxyl groups in DXP and one of its C-1 hydrogen atoms, were separately replaced with a fluorine atom and the effect of the substitution on the catalytic turnover was examined. It was found that the 1-fluoro-DXP is a poor substrate, while both 3- and 4-fluoro-DXP behave as noncompetitive inhibitors.
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wong
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Munos
authors.forename: Vidusha
authors.initials: V
authors.lastname: Devasthali
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Liu
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000378:metabolism*; D002384:Catalysis; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology*
chemical_list: D006845:Hydrocarbons, Fluorinated; D009097:Multienzyme Complexes; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases