Inhibition of dextransucrase by alpha-D-glucose derivatives.
alpha-D-Glucopyranosyl fluoride was modified at positions 2, 3, or 5 and these analogs were tested as substrates and inhibitors of dextransucrase from Leuconostoc mesenteroides B-512F. The analogs studied were 2-deoxy-2-fluoro-alpha-D-glucopyranosyl fluoride, 3-deoxy-3-fluoro-alpha-D-glucopyranosyl fluoride, 3-deoxy-3-thio-alpha-D-glucopyranosyl fluoride, and 5-thio-alpha-D-glucopyranosyl fluoride. Kinetic constants for alpha-D-glucopyranosyl fluoride were also determined. None of the alpha-D-glucopyranosyl fluorides were accepted as substrates for dextransucrase. 2-Deoxy-2-fluoro-alpha-D-glucopyranosyl fluoride, 3-deoxy-3-fgluoro-alpha-D-glucopyranosyl fluoride, and 3-deoxy-3-thio-alpha-D-glucopyranosyl fluoride were competitive inhibitors with Ki values of 63, 93, and 53 mM, respectively. The Km for alpha-D-glucopyranosyl fluoride was found to be 26 mM. The data indicate that the hydroxyl groups at C2 and C3 are important for proper binding of alpha-D-glucopyranosyl fluoride for the active site of dextransucrase and that the C3-hydroxyl probably acts as a hydrogen-bond donor.
Michiels
A G
AG
Department of Chemical Engineering, University of California, Berkeley 94720.
Wang
A Y
AY
Clark
D S
DS
Blanch
H W
HW
D001667:Binding, Competitive; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000031:analogs & derivatives*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D007700:Kinetics; D007934:Leuconostoc / Q000201:enzymology*
D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005964:Glucosyltransferases; C020025:dextransucrase; D005947:Glucose