Study of 1-deoxy-D-xylulose-5-phosphate reductoisomerase: synthesis and evaluation of fluorinated substrate analogues.
[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.
Wong
Alexander
A
Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
Munos
Jeffrey W
JW
Devasthali
Vidusha
V
Johnson
Kenneth A
KA
Liu
Hung-Wen
HW
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*
D006845:Hydrocarbons, Fluorinated; D009097:Multienzyme Complexes; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases