Potent inhibition of chitin synthase by an azasugar--investigation of synergistic effect with UDP.
We identified 6-deoxy-homoDMDP as a potent inhibitor of chitin synthase (Ki = 38 microM), displaying an uncompetitive inhibition pattern. Dual inhibition was also performed with the enzymatic reaction product uridine 5'-diphosphate in order to evaluate the concurrent effect of both inhibitors. An interaction coefficient alpha of 0.9 was found, revealing synergistic inhibition.
Djebaili
Mounira
M
Laboratoire Réactions Sélectives et Applications UMR 6519, UFR Sciences-CNRS, BP 1039, 51687 Reims 2, France.
Behr
Jean-Bernard
JB
D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D002384:Catalysis; D002687:Chitin Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016695:Glycosyltransferases / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014530:Uridine Diphosphate / Q000737:chemistry / Q000494:pharmacology*; D014539:Uridine Diphosphate Sugars / Q000737:chemistry
D004791:Enzyme Inhibitors; D014539:Uridine Diphosphate Sugars; D014530:Uridine Diphosphate; D016695:Glycosyltransferases; D002687:Chitin Synthase