Preliminary studies on the inhibition of D-sorbitol-6-phosphate 2-dehydrogenase from Escherichia coli with substrate analogues.
D-Sorbitol-6-phosphate 2-dehydrogenase catalyzes the NADH-dependent conversion of D-fructose 6-phosphate to D-sorbitol 6-phosphate and improved production and purification of the enzyme from Escherichia coli is reported. Preliminary inhibition studies of the enzyme revealed 5-phospho-D-arabinonohydroxamic acid and 5-phospho-D-arabinonate as new substrate analogue inhibitors of the F6P catalyzed reduction with IC50 values of (40 +/- 1) microM and (48 +/- 3) microM and corresponding Km/IC50 ratio values of 14 and 12, respectively. Furthermore, we report here the phosphomannose isomerase substrate D-mannose 6-phosphate as the best inhibitor of E. coli D-sorbitol-6-phosphate 2-dehydrogenase yet reported with an IC50 = 7.5 +/- 0.4 microM and corresponding Km/IC50 ratio = about 76.
Roux
Céline
C
Laboratoire de Chimie Bioorganique et Bioinorganique, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8124, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Bâtiment 420, Université Paris-Sud XI, 91405 Orsay Cedex, France.
Salmon
Laurent
L
Verchère-Béaur
Catherine
C
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006600:Hexosephosphates / Q000378:metabolism / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008359:Mannose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism / Q000494:pharmacology; D010428:Pentosephosphates / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D013403:Sugar Phosphates / Q000378:metabolism / Q000494:pharmacology
C456025:5-phosphoarabinonohydroxamic acid; D004791:Enzyme Inhibitors; D006600:Hexosephosphates; D006877:Hydroxamic Acids; D008360:Mannosephosphates; D010428:Pentosephosphates; D013403:Sugar Phosphates; C035752:sorbitol 6-phosphate; C027693:mannose-6-phosphate; C012188:arabinonate-5-phosphate; D013401:Sugar Alcohol Dehydrogenases; C022645:sorbitol-6-phosphate dehydrogenase; D008359:Mannose-6-Phosphate Isomerase; D005956:Glucose-6-Phosphate Isomerase